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Out-of-pocket expenses (OOPEs) are often regarded as the most inequitable method of paying for healthcare. In most of the countries, the majority of OOPE spent on healthcare is spent on medications, and in India, OOPE on medicines accounts for approximately 70% of total healthcare expenditure, and this expenditure was particularly high for households in rural areas and those with lower socioeconomic status. Public policy has the power to change OOPEs. We conducted a systematic review of the scientific literature to synthesize evidence on medicine‑related OOPE in the context of government and publicly financed health services and policies in India. We searched PubMed/Medline, Cochrane, Google Scholar, Scopus, and Grey Literature for English articles published between January 2000 and November 2022 using preset criteria. To conduct a literature search, PICO’s framework was used. Two authors extracted the data, and the other two appraised the quality of the articles fulfilling the inclusion criteria. We made a descriptive summary based on the main findings of every article, including any conclusions the authors draw about the significance of their findings. Out of 1597 articles initially screened, only 10 were eligible for inclusion and were published between 2006 and 2022. Overall, the study population ranged from 77 to 420 patients and 600 to approximately 125,000 households. We synthesized the findings reported by the included studies but could not compare OOPE burdens in private healthcare, and we were also unable to assess the integrity of the authors’ data collection and sources from a methodological point of view. All of the included studies reported on the burden of medicine‑related OOPE and, directly or indirectly, provided information relevant to existing or potential government interventions to reduce this burden. The available evidence indicates that OOPE on medicines represents a significant financial burden for individuals and their families, and it is essential to develop healthcare policies that provide affordable and accessible services to all citizens while minimizing the risk of catastrophic financial expenditure. • Out-of-pocket medicine costs are creating a significant financial burden on Indians. • Low public spending and no provision of free medicines, major drivers. • Public policy can largely influence healthcare costs. • Current policies - revision can decline out-of-pocket medicine costs burden. • New effective policies – development can provide affordable and accessible services.