Benign prostatic hyperplasia (BPH) is a prevalent age-related condition in men that leads to various urinary symptoms. Although current BPH treatments provide moderate effectiveness, they are often accompanied by undesirable side effects, highlighting the need for alternative therapeutic strategies. This study investigates the potential of Angelica gigas Nakai (AG), processed using hot melt extrusion (HME) to enhance its bioavailability and pharmacological activity, for the prevention of BPH. To systematically elucidate its therapeutic mechanisms, a network pharmacology approach was employed to predict the potential targets and pathways of AG, which were subsequently validated using both in vitro and in vivo BPH models. Based on the network analysis, the effects of HME-processed AG (HAG) on extracellular signal-regulated kinase (ERK) signaling were examined, and the androgen receptor (AR) pathway—closely associated with BPH—was also evaluated. HAG treatment significantly reduced prostate size and alleviated histopathological abnormalities. It also downregulated the expression of ERK and AR while increasing apoptotic markers in prostatic tissues and cells. These findings suggest that HAG exhibits anti-BPH potential in preclinical models by regulating AR/ERK signaling and promoting apoptosis, while also highlighting the value of HME technology in enhancing the effectiveness of traditional medicinal herbs.