Purpose <p>The aim of the current study was to evaluate the histological effects of photobiomodulation and topical nanohydroxyapatite on periodontal healing in immunosuppressed rats with ligature-induced periodontitis.</p> Methods <p>Thirty-six albino Wistar rats were randomly divided into six groups. Periodontitis was induced in all groups except the control. Immunosuppression was achieved using dexamethasone. All experimental groups underwent scaling and root planing followed by assigned treatments as a follow: group I, control (without any intervention); group II , periodontitis treated with scaling and root planing (SRP);group III, immunosuppressed with periodontitis treated with SRP ; group IV (immunosuppressed with periodontitis and treated by photobiomodulation using a 650 nm diode laser at 100 mW for 1 minute with energy density 12J/cm² (three sessions per week); group V ,immunosuppressed with periodontitis and local application of nanohydroxyapatite (nHAP) , and group VI , immunosuppressed with periodontitis treated with topical nHAP, and photobiomodulation.&#xa0;Histological evaluation was performed using H&amp;E and Masson’s trichrome staining after one, two &amp; four weeks for inflammation and periodontal healing . Data were analyzed using the chi-square test with significance set at p ≤ 0.05.</p> Results <p>Histological examination of the rats demonstrated significantly reduced inflammation in the group VI when compared with other experimental groups &amp; control group at all evaluation periods (P&lt;0.001). Also, group&#xa0;VI showed the best significant percentage of periodontal healing after four weeks compared with other experimental groups (P&lt;0.001).</p> Conclusion <p>Photobiomodulation combined with topical nanohydroxyapatite following scaling and root planing produced a synergistic regenerative effect in immunosuppressed rats.</p>