Human rhinoviruses (HRVs) are the primary cause of the common cold, a highly contagious upper respiratory tract infection characterized by nasal congestion, sneezing, and sore throat. HRV replication depends on its 3C protease (HRV-3Cpro), a key enzyme that cleaves the viral polyprotein into functional proteins essential for viral maturation. Currently, no FDA-approved inhibitors specifically target HRV-3Cpro. While rupintrivir, a synthetic inhibitor, advanced to clinical trials, it ultimately failed due to limited efficacy. This study investigated the potential of Vitex negundo (or lagundi)—a medicinal plant traditionally used in the Philippines for treating colds and respiratory ailments—as a source of natural HRV-3Cpro inhibitors through in silico molecular docking and pharmacokinetic (ADMET) evaluation. Fifteen phytochemicals reported from Philippine V. negundo were screened, with four compounds—agnuside (-6.9 kcal/mol), luteolin 7-O-glucoside (-6.7 kcal/mol), 2′-p-hydroxybenzoyl mussaenosidic acid (-6.6 kcal/mol), and 6′-(p-hydroxybenzoyl) mussaenosidic acid (-6.5 kcal/mol)—exhibiting stronger binding affinities than the reference inhibitor rupintrivir (-6.2 kcal/mol), suggesting potential for more effective enzyme inhibition. While agnuside had the strongest binding affinity, 6′-(p-hydroxybenzoyl) mussaenosidic acid exhibited the most favorable drug-likeness and ADMET profile, being predicted as non-mutagenic, non-hepatotoxic, and non-inhibitory to major drug-metabolizing enzymes. Nevertheless, their low oral bioavailability and gastrointestinal absorption suggest the need for alternative delivery methods to enhance therapeutic efficacy. Therefore, these findings highlight the antiviral potential of V. negundo phytochemicals as plant-based HRV-3Cpro inhibitors. Further in vitro and in vivo studies are recommended to validate their bioactivity.