Childless couples who are struggling to conceive face the risk of mental health issues, due to increased psychological distress in the form of stress, anxiety, and depression. This would adversely impact their quality of life in terms of mind-body (physical, psychological, and behavioural), emotional (tension, frustration, anger, and guilt), sociological (stigmatization, self-isolation, and social withdrawal) and relational (marital and sexual relationship) aspects. The aim of this review is to learn more about psychological distress and the quality of life among childless couples undergoing infertility treatment. The literature search was conducted using SCOPUS, EBSCOHOST, ProQuest, Ovid, and Science Direct databases for the period from 2016 to 2022, with a total of 6,001 articles retrieved. However, only six articles fulfilled the inclusion criteria applied in this review. The search was limited to studies published in the English language with cross-sectional study design only. The following medical subject heading terms were used: infertility, childless couple, psychological distress, and quality of life, with (“AND,” and “OR,”) used to narrow and widen the search. Overall, the findings show that childless couples do experience psychological distress in the form of depression, stress, anxiety, stigmatisation, low self-esteem, and social isolation; they also face psychosocial problems and thus their quality of life are impacted. Further research should focus on psychosocial aspects, such as developing effective care programs that can contribute towards the effective management of psychological and social issues faced by couples struggling with infertility.