To analyze the effect of fenestrated decompression + two-stage curettage in the treatment of giant mandibular cysts. Methods: The clinical data of 100 cases of giant jaw cysts (from January 2020 to December 2024) were retrospectively collected and divided into groups according to surgical methods (traditional curettage group, fenestrated decompression + two-stage curettage group), 50 cases in each group, and the treatment effectiveness, inflammatory factor levels, complications, University of Washington Quality of Life Questionnaire (UW-QOL) scores and disease recurrence were observed in the two groups. Results: Comparing the total effective rate, the window decompression + second-stage curettage group (96.00%) was higher than the traditional curettage group (82.00%) (P<0.05); compared with the traditional curettage group, the window decompression + second-stage curettage group 1 week after surgery The levels of interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α (TNF-α) in the surgery group were lower (P<0.05); the total incidence of complications in the window decompression + second-stage curettage group was 6.00%, lower than 22.00% in the traditional scaling group (P<0.05); comparison of UW-QOL scores in each dimension (emotion, appearance, pain, chewing, taste, saliva), window opening 6 months after surgery The decompression + two-stage curettage group was higher than the traditional curettage group (P<0.05); the recurrence rate of the window decompression + two-stage curettage group (2.00%) was lower than the traditional curettage group (16.00%) (P<0.05). Conclusion: Carrying out fenestration decompression + two-stage curettage for patients with giant jaw cysts can help suppress the inflammatory reaction, improve clinical outcomes, and enhance the quality of life.