Objective To explore the efficacy of prehabilitation strategies based on frailty assessment in the surgical treatment of elderly patients with cholelithiasis.Methods With the purposive sampling method, 66 patients diagnosed with cholelithiasis planning to receive elective surgery in the outpatient department of Hunan Provincial People's Hospital from May to September 2022, were selected and randomly divided into the control group and the experimental group, each with 33 cases. The control group received conventional perioperative treatment, and the experimental group was additionally treated with prehabilitation programs. Prehabilitation-related and perioperative indicators before and after the intervention were compared between the two groups.Results There was no difference between the two groups in sex composition, age, education degree, body mass index, the score of the FRAIL scale, the 6-minute walking distance (6MWD), or scores of Hospital Anxiety and Depression Scale (HADS) and Nutrition Risk Screening 2002 (P > 0.05). The scores of the FRAIL scale of the two groups on the day of admission, 24 hours before surgery, 5 days after surgery, and 30 days after surgery were compared, which demonstrated that there were differences in the scores of the FRAIL scale among the time points (P < 0.05) and between the two groups (P < 0.05), where those in the experimental group were lower compared with the control group, indicating higher efficacy in the experimental group. Besides, the change trends of the scores of the FRAIL scale were also different between the two groups (P < 0.05). The serum levels of albumin (Alb), 6MWD and the HADS scores in the two groups on the day of admission, 24 hours before surgery, and 5 days after surgery were compared, and the results revealed that they were different among the time points (P < 0.05) and between the groups (P < 0.05). Compared with the control group, the serum levels of Alb and 6MWD were higher, and the HADS scores were lower in the experimental group, which suggested better efficacy in the experimental group. There were differences in the change trends of the serum levels of Alb, 6MWD and HADS scores between the two groups (P < 0.05). The time to first postoperative off-bed activity and the length of hospitalization in the experimental group were shorter than those in the control group (P < 0.05). No complication or death occurred in either group during the perioperative period (P > 0.05).Conclusion For the elderly with cholelithiasis, prehabilitation strategies based on frailty assessment effectively improve the frailty, activity, nutrition, psychological status and the quality of life of patients, and promote early recovery among them.