Disclosed are a carboxymethyl-hydroxypropyl-β-cyclodextrin and preparation method thereof, the carboxymethyl-hydroxypropyl-β-cyclodextrin being a β-cyclodextrin derivative mixedly substituted by carboxymethyl and hydroxypropyl, the derivative being: n-(2, 3, 6-O-carboxymethyl)-m-(2, 3, 6-O-2-hydroxypropyl)-β-cyclodextrin. The substituted groups of each mole of cyclodextrin contain n carboxymethyl and m hydroxypropyl, m being the number of connections to hydroxypropyl in each mole of cyclodextrin derivative, that is, the average degree of substitution of hydroxypropyl, and n being the number of connections to carboxymethyl in each mole of cyclodextrin derivative, that is, the average degree of substitution of carboxymethyl, where m is a number selected from 1 to 6 and n is a number selected from 1 to 6. The present invention acts as a medical excipient, and has the features of low hemolytic property, low toxicity, and strong solubility.