Bone transplantation ranks second worldwide among tissue prosthesis surgeries. Currently, one of the most promising approaches is regenerative medicine, which involves tissue engineering based on polymer scaffolds with biodegradable properties. Once implanted, scaffolds interact directly with the surrounding tissues and in a fairly aggressive environment, which causes biodegradation of the scaffold material. The aim of this work is to experimentally investigate the changes in the effective mechanical properties of polylactide scaffolds manufactured using additive technologies. The mechanism and the rate of the degradation process depend on the chosen material, contact area, microstructural features, and overall architecture of sample. To assess the influence of each of these factors, solid samples with different dimensions and layers orientation as well as prototypes of functionally graded scaffolds were studied. The research methodology includes the assessment of changes in the mechanical properties of the samples, as well as their structural characteristics. Changes in the mechanical properties were measured in compression tests. Microcomputed tomography (micro-CT) studies were conducted to evaluate changes in the microstructure of scaffold prototypes. Changes caused by surface erosion and their impact on degradation were assessed using morphometric analysis. Nonlinear changes in mechanical properties were observed for both solid samples and lattice graded scaffold prototypes depending on the duration of immersion in NaCl solution and exposure to different temperatures. At the temperature of 37 °C, the decrease in the elastic modulus of solid specimens was no more than 16%, while for the lattice scaffolds, it was only 4%. For expedited degradation during a higher temperature of 45 °C, these ratios were 47% and 16%, respectively. The decrease in compressive strength was no more than 32% for solid specimens and 17% for scaffolds. The results of this study may be useful for the development of optimal scaffolds considering the impact of the degradation process on their structural integrity.