A study was conducted to determine the efficacy and safety of cefpodoxime proxetil (CFP) dispersible tablets in the treatment of respiratory tract infection in children and to analyze the antibacterial effect of cefpodoxime proxetil nanoemulsion (CFP-NE). A retrospective analysis was conducted on 118 children with upper respiratory tract infection who received antibiotic treatment between March 2018 and March 2021. The control group was treated with cefradine and the CFP group was treated with CFP dispersible tablets. The serum indexes and bacteriological test results of the two groups were collected before and after treatment, and the bacterial clearance rate, infection control, and occurrence of adverse reactions were observed and compared between the two groups. Cefpodoxime proxetil nanoemulsion (CFP-NE) was prepared and its surface characteristics were observed. CFP-NE and CFP were used to treat infections by multiple strains of bacteria and the antibacterial effect and minimum inhibitory concentration (MIC) of CFP-NE were observed. The bacterial strain clearance rate of the CFP group was 96.2% and the total infection control rate was 94.92%. The bacterial strain clearance rate of the control group was 88.9% and the total infection control rate was 81.36%. Serum index detection showed that antibiotic treatment could reduce serum indexes of amyloid A, C-reactive protein, procalcitonin, and other indexes and CFP had better efficacy. There were only four cases of adverse reactions after treatment with CFP, a result similar to that of other antibiotics. The prepared CFP-NE system was stable, the particles were uniform, and the diameter of the inhibitory zone against pathogenic Escherichia coli and Salmonella was larger than that of the CFP group. The MIC of CFP-NE was significantly lower than the MIC of the CFP group (P < 0.05). CFP dispersible tablets are safe and effective for the treatment of respiratory tract infection in children and the antibacterial effect of CFP-NE is greater than that of CFP.