Objective The aim of this study was to analyze the clinical characteristics of adult patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis combined with anti-myelin oligodendrocyte glycoprotein (MOG) antibodies. Methods This was a non-randomized controlled study. Clinical data were collected from 17 patients with anti-NMDAR encephalitis combined with anti-MOG antibodies admitted to Xuanwu Hospital, Capital Medical University, from January 2020 to August 2024. As controls, 20 patients with NMDAR(+)/MOG(-) and 27 patients with MOG(+)/NMDAR(-) were selected. Results The mean age of onset in the double-positive group was 33.47 +/- 1.065 years, with a male-to-female ratio of 14:3. Significant differences were observed between the NMDAR(+)/MOG(+) group and the NMDAR(+)/MOG(-) group in terms of headache, lumbar puncture pressure, and cerebrospinal fluid (CSF) leukocyte counts (P < 0.05). Comparing the NMDAR(+)/MOG(+) group with the MOG(+)/NMDAR(-) group revealed significant differences in gender, headache, mental and behavioral abnormalities, limb twitching, loss of consciousness, cognitive impairment, speech impairment, visual impairment, limb numbness, cortical/sub-cortical white matter, brainstem lesions, OB type II, and CSF leukocyte counts (P < 0.05). No statistically significant differences were found in the comparison of CSF and serum antibody titers among the three groups (P > 0.05). Conclusion NMDAR and MOG antibodies can coexist in patients with autoimmune diseases, with a predominance of young male patients. The double-positive group exhibited more severe intracranial viral infections and a higher rate of intrathecal immunoglobulin synthesis in the central tissues. Compared to the double-positive group, NMDAR encephalitis alone presented with more similar clinical manifestations, while MOG-related disease demonstrated a higher likelihood of brainstem involvement.