Background and Aims There is ongoing debate about whether oral antibiotics should be added to mechanical bowel preparation (MBP) and prophylactic intravenous antibiotics, which are routinely administered before elective colorectal surgery. This study conducted to evaluate the effectiveness and clinical value of combining oral antibiotics with MBP in reducing postoperative anastomotic leakage (AL) and surgical site infections (SSI) in elective laparoscopic colorectal cancer (CRC) surgery using a prospective randomized controlled design.Methods From January to October 2023 the Third Xiangya Hospital, Central South University, eligible patients scheduled for elective laparoscopic CRC surgery were prospectively enrolled and randomly assigned to either a study group (oral antibiotics combined with MBP) or a control group (MBP alone). All patients received routine preoperative intravenous antibiotics. Standard laparoscopic CRC radical surgery was performed by the same surgical team. Using the incidence rates of AL and SSI within postoperative 30 d as the primary outcomes, the efficacy of the two bowel preparation methods was compared, and subgroup analyses were conducted for patients undergoing right-sided colon surgery and those undergoing left-sided colon or rectal surgery.Results A total of 192 patients were enrolled, with 96 patients in each group, showing comparable baseline characteristics. The study group had significantly shorter abdominal drain retention time, total hospital stay, and postoperative hospital stay compared to the control group (all P<0.05). No significant differences were observed between the two groups in terms of operative time, intraoperative blood loss, time to first gas passage, time to first bowel movement, time to start drinking and eating, and duration of postoperative intravenous antibiotic use (all P>0.05). The study group had a lower incidence of postoperative AL compared to the control group, but the difference was not statistically significant (3.13% vs. 5.21%, P=0.718). The overall SSI rate was significantly lower in the study group than that in the control group (6.25% vs. 27.08%, P<0.001), mainly due to differences in superficial incisional SSI (2.08% vs. 11.46%, P=0.010) and deep incisional SSI (1.04% vs. 10.42%, P=0.005). No significant differences were observed in the rates of other complications, and 30-d readmission, reoperation, or mortality between the two groups (all P>0.05). Some nutritional and inflammatory markers on postoperative day 1 and 3 were better in the study group (all P<0.05). Subgroup analysis showed no significant differences in AL and overall SSI rates between the study and control groups for patients undergoing right-sided colon surgery (both P>0.05). However, for left-sided colon or rectal surgery, the study group had significantly lower overall SSI rate (6.67% vs. 35.00%, P<0.001), mainly due to differences in superficial incisional SSI (1.67% vs. 15.00%, P=0.008) and deep incisional SSI (1.67% vs. 13.33%, P=0.038).Conclusion Preoperative administration of oral antibiotics combined with MBP significantly reduces the overall incidence of SSI and promotes postoperative recovery in elective laparoscopic CRC surgery, especially in left-sided colon or rectal surgery. This bowel preparation regimen is recommended for elective laparoscopic left-sided colon or rectal surgery.