Background Lack of definitive cure for COVID-19 and the late introduction of a vaccine were responsible to push the general public to look for a remedy to treat or prevent COVID-19. The objective of this study was to evaluate patterns and factors that affect self-medication practices in Jordan during the pandemic. Methods This was a cross-sectional study using an online questionnaire that was developed, piloted and distributed to the general public via various social media platforms. The questionnaire assessed the type of drugs and treatments used to self -medicate, the reasons behind their self- medication, and the factors affecting their practices. Results A total of 1179 participants (females 46.4%) with a mean age of 32 (SD=12.5) completed the questionnaire. The overall prevalence of the use of at least one product to treat or prevent COVID-19 was 80.4 %. The most commonly used products to self-medicate were vitamin C (57.6%), followed by paracetamol (51.9%), zinc (44.8%) and vitamin D (32.5%). Female gender (odds ratio [OR]) = 1.603, working in the medical field (OR =1.697), and history of COVID-19 infection (OR =2.026) were variables associated with self-medication. The most common sources of participants’ information about drugs to prevent or treat COVID-19 were newspapers (n=519, 44.0%), followed by pharmacists (43.4%), friends (33.8%) and internet searching such as Google (30.7%). Conclusion This study identified the main drugs and supplements used during COVID-19 and the motives behind their use. It also identified the most influential source of information on the public during the pandemic. Self-medication can lead to worsening of the patient’s health and delay seeking medical advice from healthcare professionals. Efforts should be done to help mitigate risks of self-medications by active involvement of pharmacists and other members of healthcare team to refute false claims about drug, especially in the media.