A series of poly(lactic acid) (PLA) and poly(lactic acid)-based bio-composites (sisal PLA) were prepared and studied by spectroscopic and microscopic techniques as such and after immersion at room temperature in different degradation mediums (i.e., distilled and natural sea water and solutions at pH = 2, 6, and 8). In these conditions, some of their macroscopic and microscopic properties were monitored during a period of 30 days. Water absorption increased with the increasing fiber content regardless of the immersion medium. The maximum water absorption was achieved at pH = 8 (~16%), indicating a more severe action of the alkaline mediums on the samples. The diffusivity, D, of PLA decreased with the addition of fibers and acidic mediums showed higher D, indicating higher diffusivity of water through the specimens with respect to those submerged in moderate or alkaline mediums. Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) analysis evidenced a weak interaction between the PLA matrix and the sisal fibers. Very limited degradation phenomena occur in our conditions: Despite some changes in the microstructure, the PLA backbone seems to be largely resistant to hydrolysis, almost regardless of the pH value and even at the highest sisal content.