Background: Physiotherapy is routinely prescribed alongside pharmacologic treatment for chronic cardiometabolic, musculoskeletal and neurological conditions, yet its impact on objective laboratory biomarkers is less consistently reported than clinical outcomes. Objective: To systematically review clinical studies that evaluated the effect of structured physiotherapy or exercise-based rehabilitation, in comparison with usual medical care, on laboratory tests reflecting inflammation, tissue damage or metabolic status. Methods: Electronic databases (PubMed, Scopus and Web of Science) were searched for randomized or controlled clinical studies in adults that compared a physiotherapy, exercise programme plus usual medical care versus medical care alone or minimal physical therapy, and reported at least one blood or serum laboratory marker. Systematic reviews and meta-analyses on exercise, physiotherapy and inflammatory or metabolic biomarkers were also retrieved to contextualize findings. Results: Ten original clinical studies met the inclusion criteria, spanning pulmonary rehabilitation before lung cancer surgery, knee osteoarthritis, heart failure, post stroke rehabilitation, obesity, and post–myocardial infarction cardiac rehabilitation. In studies, physiotherapy programmes were associated with reductions in C reactive protein, fibrinogen, tumour necrosis factor α, interleukin 6 and matrix metalloproteinases, and with favourable changes in bone turnover and cartilage biomarkers, compared with medical care alone. Ten systematic reviews,meta analyses consistently supported an anti-inflammatory effect of exercise based interventions in chronic diseases. Conclusions: Compared with medical treatment alone, structured physiotherapy or exercise based rehabilitation generally exerts additional favourable effects on inflammatory and tissue related laboratory biomarkers, supporting its role as a disease modifying adjunct, not only a symptomatic therapy. Well-designed trials with standardized biomarker panels are still needed.