Introduction Matrix metalloproteinases (MMP's) and tribbles 3 human homolog (Trb3) are implicated in atherosclerosis. Changes in the concentration of these biomolecules signal the risk of atherosclerosis in type 2 subjects (T2DM), with or without hypertension (HT), at an early stage. Aim Our aim was to assess the relation between noninvasive arterial stiffness indices and circulating levels of MMP2, MMP9 and Trb3. Methodology The study included 144 participants divided into 4 groups: T2DM > 5 years + HT, DM + HT (n = 55), T2DM < 2 years, DM (n = 28), HT (n = 31), and healthy controls (HC) (n = 30). Anthropometric measurements and blood biochemistry profiles were established using standard protocols. MMP2, MMP9 and Trb3 were estimated using ELISA. Pulse wave velocities (PWV) and arterial stiffness indices (ASI) were measured using PeriScope(TM). Results were analysed using SPSS 21. Results MMP2, average Brachial Stiffness Index (ba ASI) (Pearson's r = 0.235, p = 0.005) and Ankle-Brachial Index (ABI) (Pearson's r = 0.225, p = 0.007) were positively correlated. Average Ankle ASI (Ank ASI) was positively correlated to Trb3 (Pearson's r = 0.184, p = 0.028), but negatively to MMP9 (Pearson's r = - 0.184, p = 0.027). In multiple linear regression, MMP2 influenced ba ASI [adjusted R-2 = 0.038; F (3) = 2.862, p = 0.039] and ABI [adjusted R-2 = 0.033; F (3) = 2.642, p = 0.052]. MMP9 influenced Ank ASI [adjusted R-2 = 0.058; F (3) = 3.912, p = 0.01]. Conclusion Arterial stiffness indices and matrix metalloproteinases conform early risk of atherosclerosis in diabetic subjects.