Glioblastoma multiforme (GBM) is considered to be the most lethal primary brain tumor. Present research work is aimed to formulate teriflunomide (TFM) loaded intranasal (i.n.) mucoadhesive microemulsion (TFM-MME) and determined its efficacy against GBM. Globule size, zeta-potential and entrapment efficiency of developed formulation were found to be 22.81 ± 0.48 nm, −22.62 ± 1.1 mV and 98.88 ± 0.39%, respectively. Potential of TFM-MME was investigated in human U-87 multiform glioblastoma (U-87MG) cell line, where 73.2 ± 0.21% cells were destroyed at 160 $\mu$g/mL dose of the drug. Finally, C max values calculated for technetium ( 99m TC) labeled TFM in brain through administration of 99m TC-TFM-MME (i.n.) and 99m TC-TFM-ME intravenous (i.v.) using gamma scintigraphy and it was found as 0.62% and 0.41% RA/g, respectively. Thus, results suggested that 99m TC-TFM-MME (i.n.) is able to improve the uptake of TFM in brain approximately by 2-folds than 99m TC-TFM-ME (i.v.). Furthermore, drug targeting index (3.5), targeting efficiency (359.10%) and direct brain transport percentage (72.16%) confirmed drug targeting to the brain via nasal route. Concurrently, TFM-MME formulation didn't reflect any changes in liver biomarkers, hematology and histopathological examination in experimental animals. Hence, developed nose-to-brain delivery of TFM-MME can be a safe and novel brain targeting tool in brain disorders.