Objective: To investigate the efficacy of laparoscopic cholecystectomy in the treatment of patients with gallstones and its effect on the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Methods: A total of 82 patients with gallstones admitted from July 2020 to July 2023 were recruited and allocated into control and observation groups using the random number table method, with 41 cases in each group. The patients were treated with laparoscopic cholecystectomy, with the anterior triangle anatomical approach to the gallbladder in the control group and the posterior triangle anatomical approach to the gallbladder in the observation group. The treatment effect and inflammatory factor levels of both groups were observed and compared. Results: When comparing the clinical outcomes of both patient groups, the key parameters evaluated included time to mobilization, duration of surgery, extubation time, and intraoperative bleeding. The observation group exhibited a significant advantage in these parameters compared to the control group (P < 0.05). Regarding the levels of inflammatory factors between the two groups before and after treatment, there was no significant difference in values before treatment. However, following treatment, patients in the observation group showed significantly lower levels of IL-6, TNF-α, and C-reactive protein (CRP) compared to the control group (P < 0.05). Conclusion: Patients undergoing laparoscopic cholecystectomy for gallstones can benefit from the implementation of the posterior triangular anatomical approach to the gallbladder, which not only enhances therapeutic efficacy but also offers significant advantages in reducing levels of IL-6, TNF-α, and CRP. Therefore, it is recommended for the widespread adoption of this treatment approach in clinical practice.