A pH-responsive amphiphilic chitosan derivative, N-lauric-O-carboxymethyl chitosan (LA-CMCh), is synthesized. Its molecular structures are characterized by FTIR, 1H NMR, and XRD methods. The influencing factors are investigated, including the amount of lauric acid (LA), carboxymethyl chitosan (CMCh), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), and N-hydroxysuccinimide (NHS), and their molar ratio, reaction time, and reaction temperature on the substitution. The degrees of substitution (DS) of the lauric groups on the -NH2 groups are calculated based on the integrated data of 1H NMR spectra. The optimum reaction condition is obtained as a reaction time of 6 h, a reaction temperature of 80 °C, and a molar ratio of lauric acid to O-carboxymethyl chitosan to N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride to N-hydroxysuccinimide of 1:3:4.5:4.5, respectively. The crystallinity and initial decomposition temperature of LA-CMCh decrease, but the maximum decomposition temperature increases. The crystallinity is reduced due to the introduction of LA and the degree of hydrogen bonding among LA-CMCh molecules. LA-CMCh could self-aggregate into particles, which size and critical aggregation concentration depend on the degree of substitution and medium pH. LA-CMCh aggregates could load curcumin up to 21.70 %, and continuously release curcumin for >200 min. LA-CMCh shows nontoxicity to fibroblast HFF-1 cells and good antibacterial activity against S. aureus and E. coli, indicating that it could be used as an oil-soluble-drug carrier.