Objectives:The aim of the present studyis to evaluate the effect of Alendronate gel (1%) in combination with Hydroxyapatite (HA) in regeneration of periodontal defects in periodontitis patients (Clinically and Radiographically). Patients and methods: Fourty patients diagnosed as stage III & grade B periodontitis with vertical bony defects and showed radiographic bone loss ≥5mm were selected from periodontology and oral medicine department faculty of dentistry Mansoura University. The patients were divided into four groups. Group (I) composed of ten patients  treated with combination of Alendronate gel (1%) with Hydroxyapatite bone graft (HA) with periodontal flap surgery. Group (II) composed of ten patients treated with Alendronate gel (1%)  alone with periodontal flap surgery, group (III) composed of ten patients treated with Hydroxyapatite bone graft (HA) alone with periodontal flap surgery. Group (IV) composed of ten patients treated by open flap debridement using minimally invasive surgical technique. Clinical periodontal parameters (plaque index PI, gingival index GI, clinical probing depth PD, clinical attachment level CAL) were taken from each patients at baseline and 6 months after treatment. Periapical radiographs were taken for each patient to evaluate the radiographic bone level change before and after treatment. The radiographs were taken at baseline and  6 months from surgery. Results:Clinical periodontal parameters were significantly improved after treatment in all treatment groups compared to the baseline. Regarding bone level there was gain in the bone level after treatment in all treatment groups with significant improvement in group I (ALN gel 1% + HA ). There was a statistically significant difference among the treatment groups between the base line and after 6 months from surgery (p value ≤0.05). Conclusions:Combination of Alendronate gel (1%) and Hydroxyapatite (HA) gave good results in the treatment outcomes as regard bone level and periodontal clinical parameters.