Abstract Background Over-the-counter (OTC) medications are sold directly to customers without requiring a doctor’s prescription. Misuse of OTC drugs is higher in adolescents and young adults than in the general population. This review is the first to narratively synthesize the factors associated with OTC drug misuse among adolescents and young adults (14-25 years old). Aim To identify the factors that are associated with OTC drug misuse among adolescents and young adults (14-25 years). Methods A comprehensive search of three electronic databases, including MEDLINE, PsycINFO and Web of Science, was conducted to retrieve publications between 1 January 1997 and 31 July 2023. The AXIS tool was used to aid critical appraisal. Papers were analysed using thematic analysis. Results Eight studies were eligible for inclusion in this narrative review We identified four key themes: motivational factors; health literacy; illicit drug use and socioeconomic status. Sensation-seeking and using OTC drugs for recreational purposes were associated with OTC misuse. Limited health literacy and lack of understanding of OTC drugs were significant factors for misusing OTC drugs. Greater use of OTC drugs at the same time as alcohol and other illicit drugs represented that they were at increased risk for misusing OTC drugs. Finally, adolescents and young adults with low income, from rural areas and with lower educational attainment were most likely to misuse OTC drugs. Conclusions Although over-the-counter medications (OTCs) encourage self-medication, their rising misuse has led to a public health problem to which nations worldwide are responding. Therefore, education and awareness among OTC drug users policy will be helpful further on strategies to prevent the misuse of OTC drugs. Key messages • This review identifies some of the factors for misusing OTC drugs, and education and awareness among OTC drug users policy may be helpful further in strategies to prevent the misuse of OTC drugs. • This review also identifies that changing the user habits and availability of OTC drugs policy may also be helpful in further strategies to prevent the misuse of OTC drugs.