Objective To explore the effect of daratumumab combined with VRD (bortezomib, lenalidomide, dexamethasone sodium phosphate) chemotherapy regimen on T lymphocyte subsets and survival rate in newly diagnosed multiple myeloma (NDMM) patients. Methods A total of 62 patients with NDMM in our hospital (from January 2022 to December 2024) were reviewed and divided into two groups according to different treatment regimen.30 patients receiving VRD chemotherapy were classified as group B, and 32 patients receiving daretuzumab combined with VRD chemotherapy were classified as group A. The therapeutic effects of the two groups were compared, as well as the bone marrow cell content, M protein content, β2-microglobulin (β2-MC), immune inflammatory indicators [platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR)], T lymphocyte subsets [CD3+, CD4+, CD4+/CD8+], progression-free survival rate and incidence of toxic and side effects before and after treatment. Results The total remission rate of group A (83.33%, 25/30) was higher than that of group B (59.38%, 19/32) (P < 0.05). After treatment, the bone marrow cell content, M protein content and β2-MC level in group A were lower than those in group B (P < 0.05). After treatment, the PLR and LMR in group A were higher than those in group B, and the NLR was lower than that in group B (P < 0.05). After treatment, the expressions of CD3+, CD4+, and CD4+/CD8+ in group A were higher than those in group B (P < 0.05). There was no significant difference in the incidence of toxic and side effects between the two groups (P > 0.05). Conclusion: Daratumumab combined with VRD chemotherapy regimen has a significant effect in the treatment of NDMM. It can effectively improve the contents of β2-MC, M protein and bone marrow cells, regulate immune inflammatory indicators and the levels of T lymphocyte subsets, and has high safety.