Alzheimer's disease (ALZ) is a neurodegenerative disease that damages neuronal cells and causes decline in cognitive abilities. Administration of cholinesterase inhibitor compounds is the primary choice in the treatment of ALZ, one of which is rivastigmine (RVT). Several routes of administration of RVT are available, such as oral and transdermal. However, in the oral route, RVT has low bioavailability, undergoes first-pass metabolism, and the presence of the blood-brain barrier (BBB) reduces the therapeutic concentration of RVT. The transdermal route is nonselective target in the brain. This study aims to combine thermosensitive mucoadhesive gel (TG) and lipid microspheres (LM) as a drug delivery system to improve the efficacy of RVT. Combining these will prevent systemic side effects of RVT and increase drug concentration in the brain. LM was formulated with varying concentrations of Compritol polymer. The results of LM evaluation showed the values of particle size, PDI, and %EE and %DL were 8.519 μm, 0.018 ± 0.004, 72.54%, and 76.43%, respectively. The TG formulation can provide a liquid form at room temperature (25 °C) and a gel at nasal temperature (35 °C). Hemolytic and HET-CAM tests confirmed TG RVT LM's safety for use. Ex vivo studies showed controlled and sustained release of TG RVT LM, and in vivo studies showed TG RVT LM a higher pharmacokinetic profile in the brain than oral formulations and injections. The Cmax was found to be 7.05 ± 0.55 μg/cm3, Tmax was 24 h, and AUC0-24, which is related to the effectiveness of brain targeting, was 225.73 μg/cm3. In conclusion, this study shows the successful development of TG RVT LM, as evidenced by improved drug delivery to the brain, which is characterized by higher concentrations of RVT in the brain compared with oral and injectable RVT, this delivery system shows potential as a future treatment for Alzheimer's disease.