Background: Among the brain-machine interfaces, neurofeedback is a non-invasive technique that uses sensorimotor rhythm (SMR) as a clinical intervention protocol. This study aimed to investigate the clinical applications of SMR neurofeedback to understand its clinical effectiveness in different pathologies or symptoms. Methods: A systematic review study with meta-analysis of the clinical applications of EEG-based SMR neurofeedback performed using pre-selected publication databases. A qualitative analysis of these studies was performed using the Consensus tool on the Reporting and Experimental Design of Neurofeedback studies (CRED-nf). The Meta-analysis of clinical efficacy was carried out using Review Manager software, version 5.4.1 (RevMan 5; Cochrane Collaboration, Oxford, UK). Results: The qualitative analysis includes 44 studies, of which only 27 studies had some kind of control condition, five studies were double-blinded, and only three reported a blind follow-up throughout the intervention. The meta-analysis included a total sample of 203 individuals between stroke and fibromyalgia. Studies on multiple sclerosis, insomnia, quadriplegia, paraplegia, and mild cognitive impairment were excluded due to the absence of a control group or results based only on post-intervention scales. Statistical analysis indicated that stroke patients did not benefit from neurofeedback interventions when compared to other therapies (Std. mean. dif. 0.31, 95% CI 0.03-0.60, p = 0.03), and there was no significant heterogeneity among stroke studies, classified as moderate I2 = 46% p-value = 0.06. Patients diagnosed with fibromyalgia showed, by means of quantitative analysis, a better benefit for the group that used neurofeedback (Std. mean. dif. -0.73, 95% CI -1.22 to -0.24, p = 0.001). Thus, on performing the pooled analysis between conditions, no significant differences were observed between the neurofeedback intervention and standard therapy (0.05, CI 95%, -0.20 to -0.30, p = 0.69), with the presence of substantial heterogeneity I2 = 92.2%, p-value < 0.001. Conclusion: We conclude that although neurofeedback based on electrophysiological patterns of SMR contemplates the interest of numerous researchers and the existence of research that presents promising results, it is currently not possible to point out the clinical benefits of the technique as a form of clinical intervention. Therefore, it is necessary to develop more robust studies with a greater sample of a more rigorous methodology to understand the benefits that the technique can provide to the population.