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Introduction Secondhand smoke (SHS) appears to be an insidious public health issue in Saudi Arabia, with a high percentage of people being reportedly exposed. In an attempt to raise awareness about this issue, we explored medical students’ level of knowledge about SHS risks, as well as their levels of exposure to SHS and the correlation between knowledge and exposure. Methods A cross-sectional study was conducted in February 2020 at the Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia. An online, modified version of a validated questionnaire was distributed among 2nd to 6th year medical students. The questionnaire mainly explored the following items: 1) exposure level to SHS; 2) impact of SHS exposure; and 3) knowledge about SHS related health risks, with calculation of a knowledge score (range: 0–8). Adequate knowledge was defined as a score ≥5 (median = 5), and associations with sociodemographic and lifestyle factors and exposure to SHS were analyzed using chi-squared and independent t-test, as appropriate. Results Of a total 416 participants, 65.0% declared having one or more smoking persons among acquaintances, 26.4% being exposed to SHS at home, and 40.1% exposed to parental smoking during childhood. Further, 79.8% reported being regularly exposed to SHS in public places. Majority of participants reported significant discomfort (53.2%) and physical symptoms (98.3%) subsequent to SHS exposure. Among the list of 8 health risks, ear infection in children (28.1%), heart attack in children (37.5%), and cognitive deficit (47.8%) were the least frequently identified. Adequate knowledge was found among 57.5% of the participants, and was higher among females and lower among participants living with their friends, compared to their counterparts (p |