Pumpkin (Cucurbita maxima) seeds are rich in bioactive compounds, including phenolics and flavonoids, which contribute to their antioxidant properties. Traditional consumption often involves aqueous preparations, such as infusions and decoctions; however, comparative evaluations of their phytochemical content, antioxidant activity, and safety remain limited. This study compares the phytochemical profiles and antioxidant activities of pumpkin seed infusions and decoctions and evaluates their subacute oral toxicity over 14 days in rats. Pumpkin seed infusion and decoction extracts were prepared using traditional aqueous extraction methods. Total phenolic and flavonoid contents were quantified using the Folin–Ciocalteu and aluminum chloride assays. Antioxidant activity was evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical scavenging method. Subacute oral toxicity was assessed in Wistar rats following daily oral administration of 200 mg/kg for 14 days. Phytochemical screening revealed that the infusion contained higher total phenolic content (7.5 ± 0.032 mg gallic acid equivalents/g dry extract) and total flavonoid content (2.72 ± 0.0018 mg quercetin equivalents/g dry extract) compared with the decoction (6.5 ± 0.026 mg gallic acid equivalents/g dry extract and 2.53 ± 0.0014 mg quercetin equivalents/g dry extract, respectively). Accordingly, the infusion exhibited higher antioxidant activity (IC₅₀ = 3.66 ± 0.03 mg/mL) than the decoction (IC₅₀ = 4.045 ± 0.02 mg/mL). No mortality or adverse clinical signs were observed in treated animals, indicating an absence of subacute toxicity at the tested dose. These findings support the traditional use of pumpkin seeds and demonstrate that their aqueous preparations, particularly infusion, exhibit antioxidant activity with a favorable safety profile. Overall, pumpkin seeds represent a promising source of bioactive compounds.