Background: Successful anterior cruciate ligament (ACL) reconstruction is highly dependent on effective tendon-to-bone healing. Excessive osteoclast activity at the bone–tendon interface can disrupt bone remodeling, impair graft integration, and increase the risk of graft failure. Modulation of osteoclast activity using pharmacological and biological agents may enhance osteointegration after ACL reconstruction.   Objective: This study aimed to evaluate the effects of alendronate and platelet-rich plasma (PRP), administered alone and in combination, on osteoclast levels at the bone–tendon junction following ACL reconstruction using a calcaneal tendon graft in a sheep model.   Methods: A randomized controlled experimental study was conducted on 28 sheep subjected to ACL A randomized controlled experimental study was conducted on 28 skeletally mature sheep undergoing ACL reconstruction with a calcaneal tendon autograft. Animals were randomly assigned to four groups (n = 7 per group): control (K0), alendronate-treated (P1), PRP-treated (P2), and combined alendronate plus PRP-treated (P3). Alendronate was administered subcutaneously at a dose of 60 μg/kg weekly for six weeks, while PRP was applied locally at the tendon–bone interface intraoperatively. Histological evaluation was performed 12 weeks postoperatively using hematoxylin–eosin staining. Osteoclasts were identified and quantified at the tendon–bone junction. Data were analyzed using the Kruskal–Wallis test followed by Dunn’s post hoc test.   Results: there was a significant difference in osteoclast counts among groups (p < 0> Conclusion: Alendronate and PRP significantly reduce osteoclast activity at the tendon–bone interface following ACL reconstruction, with a synergistic effect observed when both therapies are combined. These findings suggest that combined alendronate and PRP therapy may enhance tendon-to-bone healing and improve biological conditions for graft integration after ACL reconstruction.