Background Previous studies have assessed the prevalence and characteristics of self-medication in COVID-19. However, no systematic review has summarized their findings. Objective We conducted a systematic review to assess the prevalence of self-medication to prevent or manage COVID-19. Methods We used different keywords and searched studies published in PubMed, Scopus, Web of Science, Embase, two preprint repositories, Google, and Google Scholar. We included studies that reported original data and assessed self-medication to prevent or manage COVID-19. The risk of bias was assessed using the Newcastle–Ottawa Scale (NOS) modified for cross-sectional studies. Results We identified eight studies, all studies were cross-sectional, and only one detailed the question used to assess self-medication. The recall period was heterogeneous across studies. Of the eight studies, seven assessed self-medication without focusing on a specific symptom: four performed in the general population (self-medication prevalence ranged between <4% to 88.3%) and three in specific populations (range: 33.9% to 51.3%). In these seven studies, the most used medications varied widely, including antibiotics, chloroquine or hydroxychloroquine, acetaminophen, vitamins or supplements, ivermectin, and ibuprofen. The last study only assessed self-medication for fever due to COVID-19. Most studies had a risk of bias in the “representativeness of the sample” and “assessment of outcome” items of the NOS.