Background The evidence of the impact of online health information-seeking (OHIS) on health outcomes has been conflicting. OHIS is increasingly recognised as a factor influencing health behaviour but the impact of OHIS on medication adherence remains unclear. Objectives We conducted a systematic review and meta-analysis to examine the associations between OHIS and medication adherence. Methods We searched Medline, Embase, Web of Science, Scopus, CINAHL and Psychology and Behavioural Science Collection for studies published up to December 2020. The inclusion criteria were studies that reported the associations of OHIS and medication adherence, quantitative design, reported primary data only, related to any health condition where medications are used and conducted on patients either in clinical or community settings. A meta-analysis was used to examine the association between OHIS and medication adherence. Results A total of 17 studies involving 24,890 patients were included in this review. The study designs and results were mixed. In the meta-analysis, there was no significant association (n = 7, OR 1.356, 95% CI 0.793-2.322, p = 0.265), or correlation (n = 4, r = -0.085, 95% CI −0.572-0.446, p = 0.768) between OHIS and medication adherence. In the sub-group analysis of people living with HIV/AIDS, OHIS was associated with better medication adherence (OR 1.612, 95% CI 1.266-2.054, p < 0.001). Conclusions The current evidence of an association between OHIS and medication adherence is inconclusive. This review highlights methodological issues on how to measure OHIS objectively and calls for in-depth exploration of how OHIS affects health decisions and behaviour.