Objective To analyze the effect of loratadine tablets combined with vitamin D drops in patients with chronic spontaneous urticaria. Methods A total of 72 patients with chronic spontaneous urticaria admitted to our hospital from January to December 2023 were selected as the research objects. They were divided into control group and observation group by random number table method, with 36 patients in each group. The control group was treated with loratadine tablets, and the observation group was treated with loratadine tablets combined with vitamin D drops. The urticaria attack score, urticaria activity score, inflammatory factor level and immune factor level were compared between the two groups. Results The scores of daily attack time and daily attack frequency of urticaria in the observation group were lower than those in the control group (P <0.05). After treatment, the scores of wheal and pruritus in the observation group were lower than those in the control group (P <0.05). After treatment, the levels of IFN-γ, TGF-β, IL-4 and IL-17 in the observation group were lower than those in the control group (P <0.05). After treatment, CD3+, CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group, and CD8+ was lower than that in the control group (P <0.05). Conclusion The application of loratadine tablets combined with vitamin D drops in patients with chronic spontaneous urticaria is effective, which can effectively improve the clinical symptoms of patients, reduce inflammation, improve immune level and promote recovery.