Background and Objectives: This systematic review and meta-analysis aimed to evaluate the efficacy of xenogeneic collagen matrix (XCM) in combination with a coronally advanced flap (CAF) in the management of multiple gingival recessions and to compare its outcomes with those achieved using the conventional connective tissue graft (CTG) + CAF approach. Materials and Methods: After searching and reviewing the literature in the electronic databases PubMed/PMC, Google Scholar, ScienceDirect, Cochrane Library, and LILACS, 601 publications were found. The titles and abstracts of 543 publications were screened. After evaluating the full text of 290 publications, based on the inclusion criteria, four randomized controlled clinical trials were included in the systematic review and meta-analysis. In all the studies, the test group was treated with XCM + CAF, whereas in the control group, CTG + CAF was used. Results: Clinical attachment level (CAL), gingival recession depth (GR), keratinized tissue width (KTW), and complete root coverage (CRC) statistically significantly (p < 0.05) improved in both groups in all of the studies. Inter-group comparison showed better results in the control group in individual studies. All clinical trials reported a statistically significant (p < 0.05) decrease in surgery time and less postoperative pain in the test group. The meta-analysis of KTW (−0.438 [95% CI, −0.714 to −0.163], p < 0.002) and GR (0.35 [95% CI, 0.098 to 0.602], p < 0.001) showed a significant difference between the test and the control groups in all of the studies. CAL (0.78 [95% CI, −0.305 to 0.461], p > 0.05) showed no statistically significant difference between test and control groups. Conclusions: CTG + CAF remains the gold standard in root coverage procedures. However, XCM offers a less invasive alternative with improved patient comfort, less postoperative pain, shorter surgical time, and acceptable clinical outcomes.