Elastin is essential to accommodate physiological deformation and provide elastic support for blood vessels. As a long-lived extracellular matrix protein, elastin can suffer from cumulative effects of exposure to chemical damage, which greatly compromises the mechanical function of elastin. The mechanical properties of elastin are closely related to its microstructure and the external chemical environments. The purpose of this study is to investigate the changes in the macroscopic elastic and viscoelastic properties of isolated porcine aortic elastin under the effects of nonenzymatic mediated in vitro elastin–lipid interactions and glycation. Sodium dodecyl sulfate (SDS) was used for elastin–lipid interaction, while glucose was used for glycation of elastin. Elastin samples were incubated in SDS (20 mM) or glucose (2 M) solutions and were allowed to equilibrate for 48 h at room temperature. Control experiments were performed in 1 × Phosphate buffered saline (PBS). Biaxial tensile and stress relaxation experiments were performed to study the mechanical behavior of elastin with solute effects. Experimental results reveal that both the elastic and viscoelastic behaviors of elastin change in different biochemical solvents environments. The tangent stiffness of SDS treated elastin decreases to 63.57 ± 4.7% of the control condition in circumference and to 58.43 ± 2.65% in the longitude. Glucose treated elastin exhibits an increase in stiffness to 145.06 ± 1.48% of the control condition in the longitude but remains similar mechanical response in the circumferential direction. During stress relaxation experiments with a holding period of half an hour, elastin treated with SDS or glucose shows more prominent stress relaxation than the untreated ones.