The invention provides a lycoramine intranasal medicated nano-brain-targeting medicine and a preparation method thereof. The preparation method comprises the following steps: firstly, oxidizing chitosan by utilizing periodate to obtain hydroformylated chitosan which has a different molecular weight and has a o-dialdehyde functional group on the chitosan chain; and further oxidizing the o-dialdehyde functional group by using DMSO as a solvent and chlorous acid as an oxidant to prepare o-dicarboxyl chitosan; performing an esterification reaction between carboxylated chitosan and lycoramine to prepare the targeting medicine. The medicine can reach cerebrospinal fluid or brain through olfactory mucosa along the conjunctive tissue enveloping the periphery of the olfactory tract or the axon of olfactory receptor neurons, can bypass the blood-brain barrier to enter the central nervous system, and is directly absorbed by the brain. The medicine has the characteristics of quick response, no injection administration and liver first-pass effect prevention, and is convenient to use due to application of a quantitative device.