Health care costs in first world populations are rising, partly due to increased use of medicines. Sedentary lifestyles and global demographic ageing have contributed to this. A physically more active population could reduce the use of medicines. The aim is to analyse the relationships between physical activity level (PAL) and medication use in the Spanish population, by sexes and age groups. Methods: A cross-sectional study with 17,199 participants, from the Spanish National Health Survey 2017. A study of normality: Normality was studied using the Kolmogorov–Smirnov test. A descriptive analysis was performed to characterise the sample. Non-parametric statistical tests were used: chi-square statistics (ordinal variables) and a Mann–Whitney U test (continuous variables) to analyse intergroup differences. A correlation study was carried out—Spearman’s rho—between medication use and PAL. A multiple binary logistic regression was performed, taking medication use as the dependent variable and PAL, sex, age and social class, as independent variables. Two-sided p-values ≤ 0.05 were considered statistically significant. Results: Relationships were found between PAL and the use of medication (p < 0.001). Performing moderate and/or vigorous PA was related to a lower use of medication compared to just walking or being inactive (p < 0.05). Weak correlations were found between PAL and medication use (p < 0.001). People with a low physical activity level shown to be at higher risk of using medications. Conclusion: High levels of PA are related to lower medication use in the Spanish population. Among all population groups, physically inactive people had a higher prevalence of medication use. Future research is needed to establish causal relationships and to propose optimal physical activity doses for each population group.