Background: Health-related quality of life (HRQoL) is determined by multiple factors that include components such as spirituality and religiousness (S/R). Even though various systematic reviews have investigated the association between S/R and improved health outcomes in the most different groups, healthy young individuals are seldom addressed. The aim this study was to evalue the association between S/R and HRQoL among young, healthy individuals.Methods: Systematic review of papers published in the last ten years and indexed in four academic research databases (PubMed, Web of Science, Cochrane Library, and Scopus) and two gray literature databases. Inclusion criteria were studies assessing S/R and HRQoL using validated instruments and assessing healthy adults (i.e., non-clinical patients, not belonging to any specific group of chronic diseases), aged between 18 and 64 years old. Results: Ten out of 1,952 studies met the inclusion criteria: nine cross-sectional and one longitudinal cohort study, in which 89% of the participants were college students. Nine studies report a positive association between S/R and HRQoL, while one study did not report any significant association. The main HRQoL domains associated with S/R were the psychological, social relationships, and environment domains, while the S/R most influent facets/components were optimism, inner strength, peace, high control, hope, and happiness. Conclusions: Higher S/R levels among healthy adult individuals were associated with higher HRQoL levels, suggesting the S/R can be an important strategy to deal with adverse environmental situations even among those without chronic diseases, enhancing the wellbeing of individuals. Registration of systematic review: PROSPERO - CRD42018104047