Carboxymethyl-beta-cyclodextrin (CM-beta-CD) was introduced to obtain surface-modified nanohydroxyapatite (CM-beta-CD-HA). The results of Fourier transform infrared, X-ray diffraction (XRD), dispersion testing, X-ray photoelectron spectroscopy, and thermal gravimetric analysis showed that CM-beta-CD was surface-grafted onto nanohydroxyapatite (n-HA) by the reaction of a carboxyl group of CM-beta-CD with Ca2+ ions during the formation of n-HA. The best appropriate reaction condition was obtained, which accomplished CM-beta-CD-HA with the greatest grafting amount and best dispersion. Then, CM-beta-CD-HA was introduced to poly(lactic-co-glycolide) (PLGA) with different amounts of 5, 10, and 15 wt % by a solution mixing method, and the properties of CM-beta-CD-HA/PLGA composites were also investigated by electromechanical universal testing, XRD, scanning electron microscopy, differential scanning calorimetry, and polarized optical microscopy. The results indicated that CM-beta-CD-HA with 10 wt % had the best mechanical reinforcing effectiveness for PLGA, whose tensile strength of the CM-beta-CD-HA/PLGA composite was 14.84% higher than that of pure PLGA because of its best dispersion and promotion crystallization, suggesting that CM-beta-CD-HA obtained by the new surface-modification strategy has great potential to be used as a reinforcing filler for PLGA as a bone material in the future.