Both dyslipidemia and the development of atherosclerosis are thought to be linked to psoriasis. The formation of atherosclerotic plaques is facilitated by low-density lipoprotein (LDL) oxidation and promoted by anti-oxidized low-density lipoprotein (anti-oxLDL). Oxidized LDL (oxLDL) and anti-oxLDL levels are increased in patients with psoriasis. In this study, we evaluated oxLDL and anti-oxLDL levels in patients with psoriasis and healthy volunteers and examined the effect of methotrexate and adalimumab treatment on those levels. The study included 34 patients with psoriasis (methotrexate: 17, adalimumab: 17) and eight healthy volunteers. The serum lipid profile, anthropometric measurements, the severity of psoriasis, and cardiovascular risk were assessed in each subject. The plasma levels of oxLDL and anti-oxLDL were recorded before and after 12 weeks of treatment. During the study period, a decrease in oxLDL level was observed in patients treated with methotrexate (p = 0.02; baseline versus the end of the study). However, at baseline, the highest levels of oxLDL and anti-oxLDL were observed in the adalimumab group and the lowest in the control group (p = 0.00014). Methotrexate contributed to the reduction of serum oxLDL, which showed its anti-inflammatory effect. Understanding the effect of Methotrexate on comorbidities is crucial in selecting the appropriate therapeutic approach for patients with psoriasis.