Background and Objectives: The process of atherosclerotic plaque formation and its destabilisation is a process in which many proteins and cytokines are involved. Examples of such proteins are osteopontin (OPN), osteoprotegerin (OPG), metalloproteinases (MMPs) and myeloperoxidase (MPO). The aim of our study is to compare the concentrations of the above-mentioned markers in the plasma of patients with the confirmed presence of rupture plaque in comparison with the plasma of healthy people. Materials and Methods: The study included people suffering from dyslipidemia in whom the presence of unstable atherosclerotic plaque was confirmed by ultrasound. The concentrations of OPN, OPG, MPO, metalloproteinase 2 (MMP-2), and metalloproteinase 9 (MMP-9) in the plasma of these people were determined and compared with the concentrations of these proteins in the plasma of healthy people. Results: Levels of MMP-2, MMP-9 (p < 0.001), OPN, and OPG (p < 0.05) were statistically significantly lower in the group of healthy people than in the study group. Differences in MPO concentration were not statistically significant (p = 0.073). Conclusions: In the plasma of people with confirmed presence of rupture plaque, the concentrations of OPN, OPG, and MMPs are higher compared to the group of healthy people, which may suggest the use of these proteins as novel markers of the presence of unstable atherosclerotic plaque.