Objective To observe the effects of probiotics on the course of mild coronavirus disease 2019 (COVID-19) caused by Omicron variant. Methods A retrospective analysis was performed of the medical data of 133 COVID-19 patients admitted to the third ward of Fangcang shelter hospital located in the National Exhibition and Convention Center (Shanghai) from May 2 to May 12,2022. The patients were divided into two age cohorts:adult (18-59 years old, n=79) and elderly (≥60 years old, n=54). Each cohort was further divided into control group and probiotics group according to whether they received the adjuvant treatment of probiotics (subtilis bifunctional enteric-coated capsule). Of the adult cohort, 40 patients were in the control group and 39 in the probiotics group; of the elderly cohort, 28 were in the control group and 26 in the probiotics group. The two groups in both age cohorts were compared in negative conversion time of the SARS-CoV-2 nucleic acid, length of hospital stay, clearance rates of ORFlab gene and N gene, and relief of main symptoms. SPSS 26.0 was used for statistical analysis. According to the data type, t-test, Wilcoxon rank sum test, χ² test, or Fisher exact probability method was used for inter-group comparison. Results In the adult cohort, there was no statistically significant difference in negative conversion time of the nucleic acid, length of hospital stay, ORFlab gene clearance rate, N gene clearance rate, and relief of main symptoms between the control group and the probiotics group. In the elderly cohort, there were statistically significant differences between the two groups in negative conversion time of the nucleic acid [11.0 (9.0,13.0) vs 8.0 (6.0,10.0) d] and the length of hospital stay [10.5 (9.0,13.0) vs 8.0 (6.0,10.0) d] (P<0.05 for both), but there was no statistically significant difference in the clearance rate of ORFlab gene and N gene. The Kaplan-Meier curves showed that there was no statistically significant difference in the median conversion time between the two groups in the adult cohort (7.0 vs 6.0 d; P=0.383), and that there was a statistically significant difference in the elderly cohort (11.0 vs 8.0 d). Conclusion The adjuvant treatment of probiotics can enhance negative conversion of the nucleic acid in the elderly patients with mild COVID-19 caused by Omicron variant.