Diffuse and multi-lobes involved glioma (DMG) is a rare disease, and the aim of this study was to assess the role of multimodal-assisted surgical resection of tumours combined with chemoradiotherapy and identify prognosis. Clinical data were collected from 38 patients with a diagnosis of DMG. Nineteen patients received multimodal-assisted surgical resection of tumours combined with chemoradiotherapy, and another 19 patients underwent chemoradiotherapy alone after stereotactic puncture biopsy. The clinical characteristics, magnetic resonance imaging (MRI) findings, histopathological diagnosis, progression-free survival, and overall survival of DMG patients were retrospectively analysed. Twenty-six males and 12 females were included, and the age of the participants ranged from 10 to 80 years (46.34 ± 15.61). The median overall survival in our study was 25 months, and the progression-free survival was 17 months. The extent of resection was 50.10–73.60% (62.54% ± 7.92%). The preoperative and the postoperative KPS score of the patients in the operation group showed no statistically significant difference. The results of logistic regression demonstrated that overall survival was positively associated with operative treatment + chemoradiotherapy (p = 0.003) but negatively associated with age and corpus callosal involvement (p = 0.028 and 0.022, respectively). Kaplan–Meier analyses showed that those who underwent surgical treatment had a significant progression-free and overall survival benefit compared to those who did not undergo surgical treatment (log-rank test; p = 0.011 and 0.008, respectively). Older age and involvement of the corpus callosum represent a poor prognosis in DMG patients. Multimodal-assisted surgical resection of tumours combined with chemoradiotherapy might be a treatment option for DMG. Further research is needed to obtain the clear evidence of the effect of surgical treatment.