ABSTRACTHydrolytic degradation of a nanocomposite of poly(L‐lactic acid), PLA, and a layered double hydroxide (LDH) modified with the drug 4‐biphenyl acetic acid (Bph) has been studied. PLA/LDH‐Bph nanocomposite was prepared by solvent casting with 5 wt % of drug modified LDH and the hydrolytic degradation was carried out in a PBS solution at pH 7.2 and 37 °C. Neat PLA with 5 wt % 4‐biphenyl acetic acid was studied as reference material (PLA/Bph). The materials were studied by WAXS, TEM, TGA, DSC, SEM, FTIR, SEC and contact angle measurements. For PLA/Bph, an acid catalytic effect, caused by the drug, accelerates PLA mass loss. However, for PLA/LDH‐Bph, the presence of LDH produces a barrier effect that initially reduces the diffusion of the oligomers produced during hydrolytic degradation. DSC results demonstrate that Bph induces faster PLA crystallization and this effect is reduced in PLA/LDH‐Bph nanocomposites because of their lower drug content. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43648.