Several studies have been conducted to find at least an association between physical activity (PA)/ physical exercise (PE) and the possibility to modulate the gut microbiome (GM). However, the specific effects produced on the human GM by different types of PA/PE, different training modalities, and their age-related effects are not yet fully understood. Therefore, this systematic review aims to evaluate and summarize the current scientific evidence investigating the bi-directional relationship between PA/PE and the human GM, with a specific focus on the different types/variables of PA/PE and age-related effects, in healthy and unhealthy people. A systematic search was conducted across four databases (Web of Science, Medline (PubMed), Google Scholar, and Cochrane Library). Information was extracted using the populations, exposure, intervention, comparison, outcomes (PICOS) format. The Oxford Quality Scoring System Scale, the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) tool, and the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies were used as a qualitative measure of the review. The protocol was registered in PROSPERO (code: CRD42022302725). The following data items were extracted: author, year of publication, study design, number and age of participants, type of PA/PE carried out, protocol/workload and diet assessment, duration of intervention, measurement tools used, and main outcomes. Two team authors reviewed 694 abstracts for inclusion and at the end of the screening process, only 76 full texts were analyzed. Lastly, only 25 research articles met the eligibility criteria. The synthesis of these findings suggests that GM diversity is associated with aerobic exercise contrary to resistance training; abundance of Prevotella genus seems to be correlated with training duration; no significant change in GM richness and diversity are detected when exercising according to the minimum dose recommended by the World Health Organizations; intense and prolonged PE can induce a higher abundance of pro-inflammatory bacteria; PA does not lead to significant GM α/β-diversity in elderly people (60+ years). The heterogeneity of the training parameters used in the studies, diet control, and different sequencing methods are the main confounders. Thus, this systematic review can provide an in-depth overview of the relationship between PA/PE and the human intestinal microbiota and, at the same time, provide indications from the athletic and health perspective.