Purpose <p>Infectious complications remain a significant cause of morbidity after gastrectomy for gastric cancer. Selective decontamination of the digestive tract (SDD) is effective in colorectal surgery, but its role in upper gastrointestinal procedures is unclear.</p> Methods <p>We conducted a retrospective cohort study of patients undergoing open gastrectomy between 2014 and 2024. Patients treated with perioperative SDD (2018–2024) were compared with a matched historical cohort without SDD (2014–2018) using 1:1 propensity score matching (PSM). The primary endpoint was infectious complications.</p> Results <p>A total of 108 patients were matched (54 SDD, 54 non-SDD). Rates of major complications (16.7% vs. 14.8%), anastomotic leakage (5.6% vs. 3.7%), superficial surgical site infections (SSIs) (14.8% vs. 11.1%), and organ/space infections (7.4% vs. 13.0%) were similar between the two groups. However, pneumonia occurred significantly more frequently in the SDD group (18.5% vs. 3.7%, <i>p</i> = 0.029). Microbiological analyses revealed more enterobacteriaceae and enterococci in the SDD group, with resistant isolates detected exclusively in this cohort.</p> Conclusion <p>SDD did not reduce infectious complications after gastrectomy and was associated with higher pneumonia rates and the emergence of resistant isolates. These findings question its routine use in gastric cancer surgery and highlight the need for further prospective evaluation.</p>