Hepatocellular carcinoma (HCC) is the third leading cause of cancer death and the sixth most diagnosed cancer. Curcumin (C) has anticancer effects toward HCC and may enhance the antitumor effects of certain traditional chemotherapeutic and molecular target drugs. Co administration with piperine (P) improves curcumin’s bioavailability, while taurine (T) also exhibits antitumor properties. This study aimed to assess the potential effects of the CPT combination on biochemical and immunological parameters in HCC patients. Following the PRISMA guidelines, a systematic review and meta-analysis were conducted using data from several databases, focusing on HCC and CPT studies. Review Manager 5.4 was used to perform the meta-analysis. Four studies involving 81 HCC patients met the inclusion criteria, with three included in the meta-analysis. Over three successive 30-day cycles of CPT treatment, significant reductions were observed in biochemical parameters including AST (SMD = 1.13, 95% CI: 0.29—1.97, p = 0.008), ALT (SMD = 0.33, 95% CI: 0.13—0.53, p = 0.001), and total bilirubin (SMD = 0.65, 95% CI: 0.45—0.85, p < 0.00001), while albumin levels showed no significant change (SMD = 0.00, 95% CI: -0.33—1.34, p = 0.98). Included studies indicated significant reductions in IL-10, CD25, miR-21, VEGF, CD4+CD25+%, and CD8+CD25+%, alongside increases in IFN-γ, CD4, CD8, IL-2, and IL-12 following CPT treatment. In conclusion, CPT combination therapy induced significant improvements in biochemical and immunological parameters across three treatment cycles, highlighting its potential as a promising natural therapeutic option for HCC management. Further research is necessary to validate these findings