This retrospective case series investigated the clinical and radiographic outcomes in 19 intrabony defects treated with periodontal regenerative therapy utilizing a combined approach. Placing an amnion-chorion membrane (ACM) as a biologic modifier on the root surface of the periodontally diseased tooth, combined with bone substitutes and an additional ACM as a barrier membrane, the treated sites were examined 8 to 24 months after the therapy. The preoperative (baseline) mean probing pocket depth (PPD) was 7.21 ± 1.08 mm, and the mean clinical attachment level (CAL) was 7.68 ± 1.49 mm. A mean PPD reduction of 4.05 ± 1.22 mm, CAL gain of 3.68 ± 1.34 mm, and 73.91% ± 22.02% of bone fill were recorded postoperatively. Without any adverse events, root-surface application of ACM as a biologic material in periodontal regenerative therapy could be a safe and cost-effective approach.