(1) Background: Guided tissue regeneration was an effective surgical procedure in the management of intrabony defects and has undergone a number of changes in terms of materials and techniques. The aim of this study is to compare AmnioGuard and BioMesh in combination with NovaBone putty in intrabony defects. (2) Methodology: Ten patients who needed regenerative periodontal therapy were randomly allocated into two groups based on the inclusion criteria. These patients were subjected to phase I therapy followed by which Group A patients were treated with AmnioGuard + NovaBone putty whereas Group B with BioMesh + NovaBone putty. The clinical indices were obtained at baseline, 3 months and 6 months post-operatively while radiographic parameters were obtained at 6 months post-op. (3) Results & Conclusion: At six months after surgery, Group B (33% bone gain) showed a statistically significant change from Group A (16% bone gain) in both the clinical and radiographic measures (p < 0.05).