<p>Healthcare wastewater contains complex mixtures of pharmaceutical residues, pathogens, and antibiotic-resistant genes. If not treated effectively, these contaminants can pose a threat to public health, wildlife, and soil quality. Traditional approaches to wastewater treatment are particularly costly, energy-intensive, and often impractical in low-resource areas. This study looked to investigate a nature-based alternative using constructed wetlands (CW) with ignimbrite substrate as filter media and Cyperus alternifolius as macrophytes. Two parallel horizontal subsurface flow wetland systems (a planted and unplanted system) with hydraulic retention times (HRTs) of 4, 8, 12, and 24 days were installed for healthcare wastewater treatment. The improved performance was demonstrated by the planted system, with pollutant removals of chemical oxygen demand (COD), color, total suspended solids (TSS), and nitrate reaching up to 95.8 ± 4.2%, 98.8 ± 0.1%, 96.9 ± 1.6%, and 96.3 ± 0.8%, and, for the unplanted system, 87.5 ± 8.3%, 92.3 ± 0.7%, 92.2 ± 4.1%, and 91.6 ± 1.4% were recorded, respectively, at the longest retention time. Therefore, results from Fourier-transform infrared (FTIR) and X-ray diffraction (XRD) showed that ignimbrite was chemically bonded and structurally altered such that pollutant retention could be affected in a meaningful way. Notably, through strong natural synergy between ignimbrite and Cyperus alternifolius in constructed wetlands, the study provides an affordable and manageable mechanism for managing healthcare wastewater before discharge into the environment. It is beneficial to treat healthcare wastewater in low-resourced areas.</p>