Abstract Study question What empirical evidence exists on the well-being and psycho-social health of couples who become parents at an advanced age and their children? Summary answer Empirical evidence mostly focus on the well-being and psycho-social health of offspring (psychotic disorders, (neuro-)developmental disorders) and only little knowledge exists about their parents’ well-being. What is known already In many societies, people tend to have children at an increasingly advanced age and there is increasing attention in the medical literature towards the consequences of this trend. This systematic review is the first one to critically synthesize the existing empirical literature on the psycho-social health and well-being of parents who had their children from the age 40 onwards and their offspring. Study design, size, duration We conducted a Systematic Review and registered its protocol in Prospero (CRD42022304564). The search strategy was designed based on a Population-Context-Outcome (PCO) structure, an adaptation of the traditional Population-Intervention-Comparison-Outcome (PICO) scheme to fit the specific aims of our study. The search was conducted in six electronic databases (namely Pubmed incl. MEDLINE, Embase, Scopus, PsycInfo, CINAHL and SocINDEX) and was limited to include empirical studies published between 01.01.2000 and 31.12.2021. Participants/materials, setting, methods Studies included are empirical studies – qualitative or quantitative – where subjects were children born to 40+ parents and their parents. Studies either examined the well-being and psycho-social health of parents and/or their children or focused on the social and ethical discussions surrounding risk and benefits of advanced parental age for parents and/or the offspring. Main results and the role of chance 5’403 articles were identified, leaving 2’543 after the removal of duplicates and 98 after the screening of titles and abstracts to be included for a full-text screening. Thereafter another 30 additional articles were excluded because they did not fulfil the inclusion criteria. Simultaneously, citation searching brought up 10 additional articles to include, of which 4 were in line with the defined inclusion criteria, leading to 69 total articles included in the final sample of the present systematic review. The key results concern four aspects relevant for the research question: (1) studies show discrepancies in defining who is a parent of advanced parental age (APA); (2) there is an imbalance in the empirical evidence produced for different participant groups (e.g. mothers, fathers, offspring); (3) aspects of wellbeing (e.g. psychotic disorders, (neuro-)developmental disorders, general well-being) discussed for the specific participant group studied; and (4) a narrative synthesis of the advantages and disadvantages related to psycho-social health and wellbeing for the specific participant group. Limitations, reasons for caution Only empirical studies in English, published between 01.01.2000 and 31.12.2021 were included in this review. Also, the review focuses only on empirical evidence produced in studies where parents were 40 years or older at the time of birth. Wider implications of the findings There are many aspects of the well-being of children born by older parents which remain unknown, thus requiring more research (esp. on psychosocial wellbeing of children) to understand the (non-medico-somatic) risks and benefits of becoming parents at an older age and designing evidence-informed policies. Trial registration number Not applicable