Introduction: The rising use of e-cigarettes among university students raises concerns about their impact on academic performance, physical activity, and oral health. Understanding these associations is key to developing effective health policies. Objective: This study aimed to examine the relationship between e-cigarette use, academic performance, physical activity, and oral health among university students. Methodology: A cross-sectional study was conducted among 500 students from higher education institutions in Russia. E-cigarette dependence, physical activity, and oral health were assessed using the PS-ECDI, IPAQ, and GBI, respectively. Academic performance was based on GPA, and data were analyzed using multivariate logistic regression. Results: E-cigarette use was associated with a 32% decrease in the odds of a high GPA (OR = 0.68, p = 0.002), a 38% reduction in high physical activity levels (OR = 0.62, p < 0.001), and an increased risk of gingival bleeding (OR = 1.76, p < 0.001). Discussion: The findings support existing research on the negative effects of e-cigarettes, emphasizing their impact on student health and academic success. Conclusions: E-cigarette use negatively affects academic performance, physical activity, and oral health. Implementing targeted health policies and educational interventions is essential to mitigate these risks. © 2025 Elsevier B.V., All rights reserved.