Plant-based diets have grown increasingly popular across the globe, mainly for their health and environmental benefits. Several studies have identified a link between plant-based diets and the decreased risk of developing cardiovascular diseases, obesity, and other health issues. We systematically reviewed human interventions to identify the relationship between various plant-based food items and the gut microbiome, alongside the biochemical and anthropometric measurements as secondary findings. The study selection process was completed using the COVIDENCE platform. Overall, 203 studies were identified, of which 101 were chosen for title and abstract screening by two independent authors. Following this process, 78 studies were excluded, and the full texts and the reference lists of the remaining 23 records were reviewed using the review eligibility criteria. A manual search yielded five additional articles. In the end, 12 studies were included in the systematic review. We found evidence for short- to moderate-term beneficial effects of plant-based diets versus conventional diets (duration ≤ 13 months) on gut microbiome composition and biochemical and anthropometric measurements in healthy participants as well as obese, cardiovascular, and rheumatoid arthritis patients. However, contradictory results were observed for Enterobacteriaceae, at the family level, and for Faecalibacterium and Coprococcus, at the genus level, of gut microbiome composition. The relationship between plant-based diets and the gut microbiome, alongside their underlying metabolic and inflammatory effects, remains largely unexplored. Hence more interventional studies are needed to address these questions.