Background Dzherelo (Immunoxel) is one of the few approved immunomodulators that has been shown to produce positive treatment outcomes in patients with tuberculosis (TB). The aim of this review was to assess the effectiveness of Immunoxel used as adjunct therapy with conventional anti-TB therapy for the treatment of pulmonary TB. Methods Comprehensive search was conducted in different major databases: PubMed (MEDLINE), EMBASE (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Scopus (Elsevier). We also searched Google Scholar along with trial registries and hand-searched the reference list of identified original research as well as review articles. Conference proceedings of relevant TB and lung disease annual conferences were also screened. Two independent authors extracted outcome data using a standardised extraction form. Relative risk (RR), mean difference (MD) and standardised mean difference (SMD) with a 95% confidence interval (CI) were used as measures of effect. We assessed certainty of evidence using GRADE. Results Six clinical trials, which met the criteria for the review, were identified, and these provided data for the review. Overall results from the six trials that compared antituberculosis treatment (ATT) alone versus ATT and Immunoxel, and ATT and placebo versus ATT and Immunoxel showed an increased number of patients becoming sputum-negative in the Immunoxel group (RR 3.19; 95% CI 2.44 to 4.17; 488 participants). There was also reduction in body temperature among patients receiving Immunoxel compared to ATT alone (MD −0.20, 95% CI −0.22 to −0.18, 345 participants). However, there were no differences in body weight changes across all the studies (MD 5.65; 95% CI −0.80 to 12.11; 382 participants). Conclusion Current evidence indicates that the use of Immunoxel as an adjunctive treatment in patients with pulmonary tuberculosis has the potential to enhance the efficacy of antituberculosis treatment. However, well-designed, conducted and adequately powered clinical trials are needed to establish the effectiveness of this adjunctive treatment. Systematic review registration PROSPERO registration number: CRD42019127823