Self-medication is an important public health issue and a challenge in several European countries, particularly in Portugal. The objectives of this study were to estimate the prevalence of self-medication in a sample of Portuguese adults in the Central and Northern Region of Portugal and to identify sociodemographic and health factors associated with self-medication. Participants and Methods: A cross-sectional analytical study was performed. The sample consisted of 197 individuals from the community, central and northern Portugal, with a mean age of 38.26 ± 14.20 years and mostly female (65.0%). The data collection was accomplished through the application of a questionnaire, composed of questions of sociodemographic characterization, health context and issues related to selfmedication. Results: In the total sample, the prevalence of self-medication throughout life was 74.1% and in the last 6 months it was 59.9%. Lifelong self-medication was significantly associated with urban residence (p = 0.018). Self-medication in the last 6 months was positively correlated with age ≤25 years (OR = 3.69, 95% CI 1.04-12.14) and negatively with the residential area (rural OR = 0.36, 95% CI, 0.15-0.84). Conclusions: We observed a high prevalence of self-medication throughout the life and in the last 6 months among the northern and central communities of Portugal. Self-medication was associated with sociodemographic and health variables. The results of the present study provide evidence for the planning of interventions in the control of selfmedication in the community.