The aim of this study was to examine the level of stress and quality of life in parents of children with disabilities, including Down syndrome, autism spectrum disorders and cerebral palsy, and in parents of children diagnosed with type 1 diabetes, compared to parents of healthy children. In addition, we aimed to investigate the association between parental stress, cortisol concentrations, and advanced glycation end-products (AGEs) with parental anxiety and depressive symptomatology. A cross-sectional study was conducted between March 2018 and March 2019, including 244 parents of children aged 4 to 12 years, from Zadar County, Croatia. Socio-demographic and anamnestic data were collected, and parents completed an extensive questionnaire used for estimation of lifestyle habits, self-esteem (Rosenberg Self-Esteem Scale), and parental perception of child’s challenging behavior (Child’s Challenging Behavior Scale). Additionally, we assessed depressive symptoms (Patient Health Questionnaire-9), anxiety (Generalised Anxiety Disorder-7), general stress (Perceived Stress Scale-10) and parental stress levels (Parental Stress Scale-18), stress resilience (Brief Resilience Scale), and quality of life (Beach Center Family Quality of Life Scale; World Health Organization Quality of Life scale - Brief version). Furthermore, we measured anthropometric parameters, blood pressure, pulse, and AGEs in parents, which we considered an indicator of oxidative stress, using a noninvasive AGE Mu Reader device (DiagnOptics, Groningen, The Netherlands). Finally, cortisol concentrations were measured in five separate saliva samples collected during one working day using Salivettes (Sarstedt, Nümbrecht, Germany). Parents collected the first sample of saliva before going to bed (around 22:00) and the remaining samples were provided the next morning after awakening (at 0, 15, 30 and 60 minutes after waking up). Based on individual cortisol concentrations, derived parameters describing the cortisol awakening response (CAR) were calculated, such as the area under the curve with respect to the ground (AUCG) and the area under the curve with respect to the increase (AUCI). Chi-square test, ANOVA test or Kruskal-Wallis test, depending on the data distribution, Pearson's correlation test or Sperman's test, and multivariate linear regression were used in data analysis. Using a multivariate linear regression model, we showed an association between parenting a child with a chronic condition and AUCI. Compared to parents of healthy children, parents of children with type 1 diabetes were more likely to have lower AUCI (ß=-0.25; P=0.028), the same as parents of children with Down syndrome (ß=-0.24; P=0.040), while parents of children with autism spectrum disorder had a marginally insignificant result (ß=-0.21; P=0.081). In contrast to AUCI, AUCG was statistically significantly associated with anxiety (ß=0.21; P = 0.004) and depression (ß=0.16; P=0.034), and marginally insignificantly with general stress perception (ß=0.13; P=0.088). General psychological stress was associated with depressive symptoms (ß=0.56; P<0.001) and anxiety (ß=0.64; P<0.001), and parental stress was associated with general stress (ß=0.22; P=0.015). Parents of children with type 1 diabetes had more pronounced depressive symptoms compared to control group parents (ß=0.18; P=0.039), while parents of children with cerebral palsy had a marginally insignificantly higher depressive symptoms (ß=0.14; P=0.058). Accumulation of AGEs in the subjects' skin was associated with parental age (ß=0.42; P<0.001) and with AUCG (ß=0.22; P=0.013). Parents of children with Down syndrome and parents of children with autism spectrum disorder were more likely to have impaired family quality of life in almost all domains compared to the control group. Parents of children with type 1 diabetes were more likely to have impaired parenting perceptions (ß=-0.31; P=0.034), impaired family emotional well-being (ß=-0.27; P=0.046), and lower overall family quality of life (ß=-0.25; P=0.038). A negative association was found between depression and the parenting domain (ß=-0.26; P=0.045), physical-material well-being (ß=-0.31; P=0.012), and overall family quality of life (ß=-0.23; P=0.042). Perception of the overall individual quality of life was impaired in parents of children with autism spectrum disorder (ß=−0.16; P=0.024) and in parents of children with cerebral palsy (ß=−0.13; P=0.040). Parents of children with autism spectrum disorder were more likely to have disturbed social relationships (ß=-0.19; P=0.026), while the environment domain was negatively associated with the parenting of children with cerebral palsy (ß=-0.16; P=0.010). Self-esteem was associated with the psychological domain of the individual quality of life (ß=0.59; P<0.001), social relationships (ß=0.42; P<0.001), the domain of physical health (ß=0.27; P=0.001), and environment (ß=0.26; P=0.001). Furthermore, self-esteem was associated with better family interaction (ß=0.38; P<0.001), parenting (ß=0.23; P=0.013) and overall family quality of life (ß=0.24; P=0.003). General stress perception was negatively associated with all domains of family and individual quality of life. The results of this study show that parents of children with chronic conditions had altered CAR and impaired quality of life, which puts them at increased risk for adverse health outcomes. These findings also provide important guidelines for future research, and point to the need for provision of additional help and support to parents caring for children with chronic health problems. Most importantly, the results of this study emphasize the need for developing suitable interventions for the appropriate coping with stress in these parents. This could result in slowing down of aging process, prevention of further health deterioration and ultimately in decreasing risks for development of chronic diseases in parents of children with chronic conditions. Nurses could have an important role in these interventions.