Brain drug delivery poses a significant challenge due to the blood-brain barrier’s extremely reduced permeability to most molecules, making it a considerable obstacle for the effective treatment of neurological and psychiatric diseases. Furthermore, conventional pharmaceutical formulations tend to lead to low drug targeting, leave drugs susceptible to enzymatic and chemical degradation, and do not easily reach high drug strength in liquid and semisolid preparations. To tackle these issues, intranasal nanoemulgels were developed, for direct nose-to-brain drug delivery, and overall improved therapeutic efficacy and safety. Nanoemulgels containing antiepileptic drug molecules phenytoin and fosphenytoin, and nanoemulgels loaded with a repurposed anti-inflammatory drug for brain cancer treatment, were produced through spontaneous emulsification, using a mixture of pre-selected oils, surfactants, co-surfactants, co-solvents and aqueous solutions of a thermosensitive gelling polymer, Poloxamer 407. Formulations were optimized and characterized in what concerned their droplet size, polydispersity index, zeta potential, pH, osmolality, stability, viscosity and rheologic behavior, in vitro drug release, and in vitro therapeutic efficacy and safety. Results showed that low droplet sizes (between 20 and 200 nm) and reduced PDI values (< 0.3) were obtained, as well as high drug strengths. The nanoemulgels depicted a pseudoplastic non-Newtonian rheological behavior, with gelling temperatures adequate for intranasal delivery (bellow the mean nasal temperature, 32 ºC). An overall high controlled cumulative drug release was also obtained (around 80% or higher after 24 hours), and in vitro therapeutic efficacy in glioblastoma cell lines proved that the developed nanoplatforms had improved anticancer effects. Hence, intranasal nanoemulgels with ideal physicochemical characteristics and preliminarily proven therapeutic effects for the treatment of different brain diseases were successfully developed. Assays in in vivo models might further confirm their potential, and their simple and cost-effective production method might catapult these nanocomposites into easing their way to industrial production.