This study had the purpose to analyse the antiviral drug acyclovir employing a voltammetric method that permits its quantification sensitively and reliably in pharmaceutical preparations. This investigation consisted of optimizing the voltammetric parameters and involved the chemical modification of the electrode. Among Au, Pt, and GC electrodes, the latter showed the best behaviour, which was modified by means of electrochemical and chemical pretreatments, using 0.10 M LiClO4 as supporting electrolyte, 20.0 mM pyrrole, and 1.0 mM acyclovir as templating species. Polypyrrole was then overoxidized in 0.10M phosphate buffer at 0.95 V vs Ag/AgCl. This approach enhanced the limit of quantification, the stability, and sensitivity. The glassy carbon electrode coated with molecularly imprinted, overoxidized polypyrrole (OPPy) behaves as a cation exchanger due to dedoping and loss of conjugation. Square wave voltammetry allowed determining acyclovir in 0.10 M phosphate buffer, pH 4.00. The pulse height and frequency were 40 mV and 50 Hz. The limit of detection was 0.20 μM. Its quantitation in a pharmaceutical preparation by multiple addition of standard, a content of (206.0 ± 4.2) mg was determined, R2 was 0.9986; the amount of Acy was 200 mg. The voltammetric method is of easy application, less expensive, and as sensitive as HPLC.