Physical activity (PA) is emerging as a safe and effective tool in the prevention and treatment of psychiatric disorders. PA subtypes include aerobic, resistance, flexibility, neuromotor (involving balance, agility and co-ordination), mind-body (e.g. tai chi, qi gong and yoga) and mixed type trainings. Evidence from clinical trials suggests that PA subtypes can have positive clinical effects, however the effects on the symptomatology may vary according to the PA subtype. It therefore stands to reason that various PA subtypes may modulate the immune system and neuroplastic processes differently. This systematic review aims to assess the immunomodulatory and neuroplastic profiles of various PA subtypes, particularly in unipolar depression and age-related cognitive decline (ARCD). The literature suggests several unique immunomodulatory and neuroplastic profiles for PA subtypes (i.e. resistance, aerobic and mind-body) in depression and ARCD. In depression, levels of various cytokines at baseline may predict treatment response to subtypes of PA and pharmacological agents. The pro-neuroplastic effects of resistance and aerobic PA in ARCD may differ due to variances in neurotrophin profiles. At this stage of literature in the field, it is difficult to draw firm conclusions on the specific immunomodulatory and neuroplastic pathways involved in these PA subtypes given of the small number of comparative studies and methodological heterogeneity between studies (e.g. study population age and illness severity, as well as duration and intensity of PA intervention). This important field requires well-designed, high-quality comparative studies to better describe unique immunomodulatory and neuroplastic profiles.