Using muscle oxygenation to evaluate the therapeutic effects of physical exercise in pathologies through near-infrared spectroscopy (NIRS) is of great interest. The aim of this review was to highlight the use of muscle oxygenation in exercise interventions in clinical trials and to present the technological characteristics related to the equipment used in these studies. PubMed, WOS, and Scopus databases were reviewed up to December 2021. Scientific articles that evaluated muscle oxygenation after exercise interventions in the sick adult population were selected. The PEDro scale was used to analyze the risk of bias (internal validity). The results were presented grouped in tables considering the risk of bias scores, characteristics of the devices, and the effects of exercise on muscle oxygenation. All the stages were carried out using preferred reporting items for systematic reviews and meta-analyses (PRISMA). The search strategy yielded 820 clinical studies, of which 18 met the eligibility criteria. This review detailed the characteristics of 11 NIRS devices used in clinical trials that used physical exercise as an intervention. The use of this technology made it possible to observe changes in muscle oxygenation/deoxygenation parameters such as tissue saturation, oxyhemoglobin, total hemoglobin, and deoxyhemoglobin in clinical trials of patients with chronic disease. It was concluded that NIRS is a non-invasive method that can be used in clinical studies to detect the effects of physical exercise training on muscle oxygenation, hemodynamics, and metabolism. It will be necessary to unify criteria such as the measurement site, frequency, wavelength, and variables for analysis. This will make it possible to compare different models of exercise/training in terms of time, intensity, frequency, and type to obtain more precise conclusions about their benefits for patients.