Background and Objectives: Gingival recession (GR) is a recognized periodontal condition that can expose the tooth root, imposing aesthetic, functional, and hypersensitivity concerns. We conducted this study to investigate xenogenic soft tissue substitutes as potential alternatives to the gold standard connective tissue graft (CTG) for the treatment of multiple GR. Materials and Methods: This systematic review and meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO. A comprehensive search of PubMed, Web of Science, Scopus, and the Cochrane Library was conducted until October 2025 for randomized controlled trials (RCTs) comparing connective tissue graft (CTG) to xenogeneic substitutes (XCM or P-XADM) for treating multiple gingival recessions. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using the RoB 2 tool, 2019 version. Data were pooled using a random-effects model to calculate mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) for primary (mean root coverage, MRC; complete root coverage, CRC) and secondary outcomes (clinical attachment level, CAL; keratinized tissue width, KTW; gingival thickness, GT; probing depth, PD). Results: Sixteen RCTs (632 patients, 1878 recessions) were included. At 6 and 12 months, CTG demonstrated a significantly greater MRC than both XCM (MD −13.4% and −11.05%) and P-XADM (MD −11.63% at 12 months). CTG was also superior to XCM in achieving CRC at 6 months (RR = 0.71, 95% CI [0.62 to 0.82]). For secondary outcomes, CTG showed superior gains in CAL and KTW at 12 months compared with both xenogeneic materials. GT was significantly greater in the CTG than in the XCM group in 12 months. No significant differences were found in PD at all time points. Conclusions: CTG continues to have superior clinical outcomes in the treatment of multiple GR. However, xenogenic materials are a promising alternative, particularly when patient comfort and satisfaction are prioritized. Future well-designed trials with larger sample sizes and standardized outcomes are needed to validate their clinical benefits and long-term stability.