Electronic cigarettes (e-cigarettes) are nicotine delivery devices promoted as a safer alternative to traditional smoking; however, their long-term health effects remain uncertain. Their use is rapidly increasing worldwide, particularly among young adults. In Jeddah, Saudi Arabia, there is limited information on e-cigarette usage among college students. This study aimed to assess the level of knowledge and awareness regarding the health effects of e-cigarettes among college students in Jeddah through a cross-sectional, survey-based study conducted in 2024 with 438 participants. Data were collected using a pre-validated self-administered questionnaire distributed via various social media platforms. Categorical variables were compared using the chi-square test. Results indicated that 54.8% of respondents reported previous smoking experience. Among the participants, 29.7% believed that e-cigarettes are an effective smoking cessation method, 50.5% viewed them as a potential replacement for traditional cigarettes, and 43.2% considered e-cigarettes a gateway to conventional smoking. Overall, 39.3% of respondents demonstrated good knowledge about e-cigarettes, with significant differences observed between age groups, genders, smoking experience (P < 0.001), and educational levels (P < 0.002). Additionally, 54.3% of respondents expressed a negative attitude toward e-cigarettes, with statistically significant differences across groups (P < 0.001). Given the relatively high prevalence of smoking among college students in Jeddah and their overall insufficient knowledge about e-cigarettes, these findings underscore the urgent need to raise awareness about the risks associated with e-cigarette use and to implement appropriate regulatory measures.