Regular physical activity (PA) has multiple beneficial effects on students’ health, effectively reducing the risk of various non-communicable diseases. Various factors play a role in an individual’s motivation to engage in and maintain regular PA. So far, no research dealing with the motives and barriers for regular PA among medical students has been conducted in the countries of the Western Balkans. The aim of this study was to identify the motives and barriers related to regular PA and compare them with different demographic, socioeconomic, and individual lifestyle factors among Western Balkans medical students. The research was conducted in a form of a cross-sectional study. It included 2452 medical students from 14 faculties in five countries (Slovenia, Croatia, Bosnia and Herzegovina, North Macedonia, and Serbia). The most commonly reported motive of medical students for regular PA is to feel better, followed by stress reduction, to look better, the desire to lose weight, and to control chronic disease. PA improvement motives are more frequently associated with the female gender, more advanced years of study, a normal weight, above average household income, and a non-smoking status. Faculty obligations are the most common barrier for regular PA among medical students, followed by other barriers, such as financial situation, current life situation, and health conditions. Barriers are more frequently reported by male students who are overweight or obese, who have a below average income, and are smokers. It is necessary for public health authorities to examine and take into account the perceived motives and barriers when forming activities and policies that aim at increasing the level of PA, in order to enhance the health of the student population.