Background: Neoadjuvant fluoropyrimidine (5FU or capecitabine)-based chemoradiotherapy (CRT) has been considered the standard of care for locally advanced rectal cancer (LARC). Whether addition of oxaliplatin (OXP) will further improve clinical outcomes is still unclear. Methods: To identify clinical trials combining oxaliplatin in preoperative CRT or perioperative chemotherapy for LARC published until December 2019, we searched PubMed, the Cochrane Library. We also search for relevant ASCO conferences. Primary endpoint was Disease-Free-Survival (DFS). Data were extracted from every study to perform a meta-analysis using Review Manager (version 5.3). Results: A total of 7 Randomized Clinical Trials (ACCORD-12, CARO-AIO-04, FOWARC, JIAO, NSABP, PETACC-6 and STAR-01) with 5782 stage II or III rectal cancer patients were analysed, including 2727 patients with OXP + 5FU regimen and 3055 patients with 5FU alone regimen. Compared with 5FU-based regimen group, OXP-based regimen group improved DFS (HR = 0.90, 95% CI: 0.81−0.99, P = 0.03) and increased pathologic Complete Response (OR = 1.21, 95% CI: 1.07−1.37, P = 0.002). Patients treated with OXP-regimen had significantly less metastatic disease (OR = 0.79; 95% CI, 0.67 to 0.94; p = 0.007). Considering Adverse Events (AEs), there was more grade 3-4 diarrhoea with OXP (OR = 2.41, 95% CI: 1.74−3.32, P < 0.00001). However, there were no significant differences grade 3-4 haematologic AEs (OR = 1.16, 95% CI: 0.87−1.57, P = 0.31). Conclusions: Combining oxaliplatin with capecitabine or 5FU in preoperative chemoradiotherapy or perioperative chemotherapy seems beneficial significantly and improved DFS. It remains necessary to identify which patients benefit most from the addition of oxaliplatin.