Abstract Probiotics play a beneficial role in improving the intestinal microecological balance and improving the health level and state of the host. In this study, cyclophosphamide was used to establish an immunocompromised mouse model. In the experiment, sixty mice were randomly divided into 5 groups: normal control, model control, Glory LP16 low-dose control (2 × 106 CFU/mouse, LP), Glory LP16 medium-dose control (2 × 107 CFU/mouse, MP), and Glory LP16 high-dose control (2 × 108 CFU/mouse, HP). The mice were tested for body weight, immune organ indexes, cellular immunity indexes, humoral immunity indexes, non-specific immunity indexes, colonic histopathological notices, intestinal flora, and short-chain fatty acids. The results showed that compared with the model control, the high-dose control showed an increase in body mass gain, thymus index, spleen index, optical density index, foot-plantar thickness, number of hemolyzed vacuoles, number of antibody accumulation, NK cell activity, carbon profile phagocytosis index, macrophage neutral red phagocytosis rate, macrophage phagocytosis index, the morphology of colon tissue tended to be more like that of the normal tissue, the regulation of the intestinal bacterial flora imbalance, and an increase in short-chain fatty acids of the intestine. It is hypothesized that Lacticaseibacillus paracasei Glory LP16 has the function of enhancing immunity in mice.