The purpose of the study was to clarify the independent association between sedentary behavior and physical activity with multiple chronic diseases and medicine intake in older individuals. Sedentary behavior and physical activity were measured by questionnaires. Diseases and medication use were self-reported. Poisson’s regression was adopted for main analysis, through crude and adjusted prevalence ratio and confidence interval of 95%. For men, sedentary time >4 hr/day presented a 76% higher prevalence of ≥2 chronic diseases, while physical inactivity increases the likelihood of using ≥2 medicines in 95%. For women, sedentary behavior >4 hr/day presented an 82% and 43% greater prevalence for ≥2 chronic diseases and the intake of ≥2 medicines, respectively. Sedentary behavior represents an independent associated factor of multiple chronic diseases in older men and women. In addition, inactivity for men and sedentarism for women are associated with the amount of medicine intake.