(1) Background: Oxidative stress (OS) has been extensively associated with male infertility, contributing to its pathophysiology in approximately 30–80% of affected individuals. Excessive reactive oxygen species (ROS) levels trigger a cascade of interconnected processes, including lipid peroxidation, DNA damage, and mitochondrial dysfunction, ultimately impairing sperm quality. (2) Methods: The present study was designed to examine the relationship between seminal oxidative stress biomarkers such as superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) and sperm DNA integrity in men with unexplained (UMI) and idiopathic (IMI) male infertility. The study population comprised 235 participants, who were divided into three groups: fertile controls (n = 78), UMI (n = 88), and IMI (n = 69). Semen analysis was performed according to WHO criteria. Sperm DNA fragmentation index (DFI) was assessed using the TUNEL assay, while sperm decondensation index (SDI) was evaluated by aniline blue staining. Seminal OS biomarkers were measured in seminal plasma using spectrophotometric methods. (3) Results: DFI and SDI were significantly increased in infertile groups compared with fertile controls (p < 0.001), exceeding the clinical thresholds of 30% and 15%, respectively. Antioxidant enzyme activities (SOD and CAT) were significantly reduced, whereas MDA levels were significantly elevated, particularly in the IMI group (p < 0.001). Correlation analysis revealed strong positive associations between MDA and both DFI (r = 0.76, p < 0.001) and SDI (r = 0.80, p < 0.001). Additionally, MDA, DFI, and SDI were negatively correlated with semen parameters, whereas SOD and CAT were positively correlated with sperm quality (p < 0.001). (4) Conclusions: Our findings emphasize the critical role of oxidative stress and sperm DNA integrity as potential biomarkers for the diagnosis and evaluation of UMI and IMI.