To compare the efficacy and safety of flexible ureteroscopy (FURS) and mini percutaneous nephrolithotomy (mPCNL) in the treatment of renal stones of 23 cm in patients with diabetes mellitus.Methods  The clinical data of 152 patients with 2-3 cm kidney stones combined with diabetes who received FURS or mPCNL in our hospital from January 2021 to July 2022 were retrospectively analyzed. Among them, 48 patients received mPCNL treatment (mPCNL group) and 104 patients received FURS treatment (FURS group). The general data, stone related data, perioperative indexes, complication rate, stone clearance rate and total hospitalization cost were collected and compared.Results  The operative time of mPCNL group was shorter than that of FURS group, the postoperative hospitalization time was longer than that of FURS group, the surgical cost and the number of operations were less than that of FURS group, and the immediate postoperative stone clearance rate was higher than that of FURS group, with statistical significance (all P<0.05). In mPCNL group, 15 patients (31.25%) achieved complete catheterization, and in FURS group, all patients had intraoperative ureteral stent indwelling. There were no major intraoperative complications (including small ureteral perforation) in either group. The mPCNL group had more postoperative complications than FURS group, and Clavien grade Ⅰ and Grade Ⅱ were the most common complications. Postoperative fever required antibiotic treatment in 5 patients in the FURS group and 11 in the mPCNL group. One patient in the mPCNL group required blood transfusion due to a significant decrease in hemoglobin, and the patient still had a progressive decrease in hemoglobin after transfusion, so super-selective renal artery embolization was performed. In mPCNL group, 2 patients had ureteral stent displacement after operation, and all of them were re-indwelled under intravenous anesthesia. For renal pelvis stones or subcalyceal stones, the immediate postoperative stone clearance rate in mPCNL group was higher than that in FURS group [50.0% (25/50) vs.86.7% (13/15), 38.9% (7/18) vs.90.0% (9/10), P=0.011, 0.009].Conclusions  mPCNL is equally effective as FURS in diabetes mellitus patients with 2-3 cm renal stones. However, FURS offers advantages with a lower complication rate, while mPCNL was comparatively superior in terms of operation time, tubeless rate and overall costs.