The novel coronavirus disease (COVID-19) pandemic has affected several countries worldwide, resulting in a considerable strain on healthcare systems and increased trend of self-medication practices. This study aims to evaluate the awareness of COVID-19 and the prevalence of self-medication during the pandemic among residents in Mogadishu, Somalia. A cross-sectional study was conducted using a structured and pretested questionnaire between May 2020 and January 2021. Participants from various disciplines were randomly recruited within the study location and interviewed about their self-medication practices during the pandemic. Descriptive statistics were used to summarise the respondents’ information and responses to the questionnaire items. Associations between participants’ demographic characteristics and specific items relating to self-medication practices were analysed using the Chi-square test. A total of 350 residents participated in the study. Approximately 63% of the participants reported having practised COVID-19 related self-medication with the main reasons being pharmacists’ advice (21.4%) and having an old prescription (13.1%), whereas 37.1% did not report their reasons for self-medication. Most participants (60.4%) engaged in self-medication despite not having any symptoms and 62.9% had taken antibiotics in the last three months. Most participants were aware that no medication has been approved for COVID-19 (81.1%), the negative effects of self-medication (66.6%), and the transmission routes of the virus. Meanwhile, more than 40% of the participants have not worn a mask while outside their homes, and do not follow the international COVID-19 guidelines. The most prevalent drug used by participants for self-medication against COVID-19 was paracetamol (81.1%) and antibiotics (78%). The factors associated with awareness of COVID-19 and self-medication practices included age, gender, educational qualification, and occupation. This study revealed considerable high self-medication practices among Mogadishu residents, thus highlighting the need to promote awareness regarding the adverse effects of self-medication and sanitisation guidelines in addressing COVID-19 at the community level.