Nanocomposite-based drug delivery systems with intrinsic controlled release properties are of great interest in biomedical applications. We report a novel polylactic acid (PLA)/halloysite nanotube (HNT) nanocomposite-based drug delivery system. PLA/HNT nanocomposites have shown immense potential for use in biomedical applications due to their favorable cyto- and hemo-compatibility. The objective of this study was to evaluate the release of active pharmaceutical ingredients (API) from PLA/HNT composites matrix and the effect of preloading the API into the lumen of the HNT on its release profile. Aspirin was used in this study as a model drug as it is a common nonsteroidal anti-inflammatory and antiplatelet agent widely used for various medical conditions. These two types of drug-loaded PLA/HNT nanocomposites were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), surface wettability and mechanical testing. Statistical analysis was conducted on numerical data. Drug entrapment and in vitro drug release studies were conducted using UV spectrophotometry. Results indicate that aspirin was successfully loaded into the lumen of HNT, which resulted in the sustained release of aspirin from the nanocomposites. Furthermore, the addition of HNT into the polymer matrix increased the mechanical properties, indicating its suitability as a drug-eluting reinforcing agent.