Safe dispensing of coronavirus disease 2019 (COVID-19) oral antivirals requires comprehensive patient assessment to identify and address significant medication-related problems (MRPs). Given the fast-paced environment of community pharmacies and limited access to outside patient records, there are challenges with pharmacists ensuring the safe and appropriate dispensing of these medications. An independent community pharmacy in Pennsylvania developed and implemented a COVID-19 oral antiviral assessment protocol to systematically review all prescriptions dispensed for nirmatrelvir/ritonavir (Paxlovid™) and molnupiravir (Lagevrio™) to identify and address MRPs. A retrospective review was conducted to assess documented MRPs, including significant drug–drug interactions and inappropriate dosing requiring intervention, for prescriptions dispensed from 9 February 2022 to 29 April 2022. Pharmacists identified one or more significant MRPs requiring intervention on 42 of the 54 nirmatrelvir/ritonavir prescriptions (78%) and 0 of the 7 molnupiravir prescriptions. Most pharmacist interventions involved drug–drug interactions between nirmatrelvir/ritonavir and HMG-CoA reductase inhibitors and calcium channel blockers, along with four renal dose adjustments for nirmatrelvir/ritonavir. This study highlights the ability of community pharmacists to identify and address MRPs and promotes the use of a protocol to encourage safe dispensing practices for medications prone to MRPs.