Introduction: This observational study was conducted to assess the knowledge, attitudes, and perceptions (KAP) of Malaysians toward participating in clinical trials. It also aimed to look for factors that will influence people’s willingness to participate in trials. We planned and developed future outreach, education tools, and recruitment strategies to increase clinical trial enrolment. Methods: A cross-sectional study was carried out on a randomly selected sample of 398 Malaysian literate adults. An online questionnaire was created and distributed to the respondents. Descriptive statistics were presented in the form of frequency and percentages. The chi-square test was employed to find the association between independent variables. Results: The majority had good knowledge (61.3%) and high awareness (88.7%) of clinical trials. However, most of them were not willing to take part in a clinical trial if they were assigned to a group of unlicensed drugs (90.2%) or randomly assigned (66.1%). The main reasons for participating in trials were recommendations from doctors (46.5%) and the potential for their own benefit (45.7%). Younger age was positively associated with the necessity and confidentiality of clinical trials. Most respondents indicated negative perceptions towards the safety of clinical trials regardless of demographic variables. Conclusion: We gained a better understanding of Malaysian people who are potential participants in a future clinical trial. These findings could help clinical researchers improve their understanding of the participants and develop effective outreach strategies for clinical trial recruitment and retention.