Although physical exercising is promoted as a protective factor against substance use and misuse (SUM), little is known about the association between participation in recreational fitness sports and SUM. This study aimed to evidence the prevalence of SUM among recreational athletes, and to define associations between certain activity-related factors and SUM. The sample comprised 760 recreational-fitness athletes (470 males and 290 females; 33.41±4.5 and 32.11±6.9 years of age for males and females, respectively). The variables included socio-demographic variables, recreational-activity-related factors (experience, programme of participation), and SUM data (cigarette smoking, binge drinking and dietary supplement usage). The consumption of cigarettes and alcohol in recreational fitness athletes is lower than the prevalence reported for the overall population. Males are more oriented to binge drinking (KW = 19.95; p < 0.01), while smoking is more common among females (KW = 54.33; p < 0.01). Moreover, there is an evident relationship between programme preferences and the consumption of substances. In females, participation in group training (dance aerobics, Pilates) is recognised as a risk factor for cigarette smoking, while the lowest incidence of SUM is revealed in those females involved in cardio-fitness training. Although our results support the hypothesis that recreational sport is protective against SUM, it seems that the leading motives for physical exercising should be regarded as the most important factors influencing SUM.