Mesoporous silica nanospheres (MSN) was prepared by hydrolysis and polycondensation of tetraethyl orthosilicate (TEOS) using N-hexadecyltrimethylammonium bromide (CTAB) as a template. The dual drug delivery system (Flu-G-Ins-MSN) was prepared by surface aminopropylation, phenylboration, cyclic adenosine monophosphate (cAMP) loading and gluconate insulin capping. The surface micromorphology, chemical structure, pore structure and surface charge were characterized by TEM, FTIR, XRD, N2 adsoorption-desorption, Zeta-potential analysis. Effect of stirring time on drug loading was examined. The effect of sugar sources, sugar concentration and pH on the release of insulin and cAMP was investigated. The results demonstrated that when the mass concentration of silica spheres was 10 g/L, the concentration of cAMP was 0.1 mmol/L, the drug loading could reach 25.9 μmol/g after stirring for 24 h. The release of glucose-triggered insulin and cAMP was significantly pH-dependent and increased with increasing pH. In the normal human physiological pH 7.4 environment, fructose and glucose exhibited the strongest stimulatory response to drug-loaded particles. Insulin release from 2 mg/mL drug-loaded particles stimulated with 50 mmol/L glucose for 0.5 h was up to 8.35 μmol/L, while the cAMP release for 20 h was up to 75%. The intermittent release experiments showed that glucose enables repeated stimulation of the uncapping for drug-loaded particles, and thus achieving a sustained controlled release of insulin and cAMP.