Objectives: We sought to investigate the healing efficacy of thermosensitive in situ gelling formulation containing metronidazole and diclofenac potassium on ligature-induced periodontitis (LIP) in rats. Methods: We used 30 adult male Sprague-Dawley rats; 24 rats were subjected to LIP, while the remaining six rats were used as control. The 24 rats with LIP were subdivided into four groups of six rats each. Group 1 received 5% metronidazole loaded gel, group 2 received 0.2% diclofenac potassium loaded gel, group 3 received 5% metronidazole and 0.2% diclofenac potassium, and group 4 (the control group) did not receive any treatment. Treatment was administered on day 0, and the rats were monitored over seven days. Specimens were collected for histological examination to assess the healing process. Results: We found a statistically significant difference (p < 0.050) in the inflammatory and repair parameters of the healing process between different treatments. Combining the two drugs significantly accelerated the healing compared to the drugs given alone. Conclusions: Using a combination of diclofenac and metronidazole could potentially accelerate the healing process compared to the use of a single drug of either diclofenac or metronidazole.