The study aimed to prepare green nanoemulsion (GNE) multi-components ((water/dimethyl sulfoxide–transcutol/isopropyl alcohol/capmul MCM C8 (CMC8)) to remove rifampicin (RIF) from a contaminated aqueous bulk solution. Pseudo ternary phase diagrams dictated several batches of GNE prepared following the reported method. Selected nanoemulsions (NF1–NF5) were characterized for morphology, globular size, size distribution (polydispersity index, PDI), viscosity, zeta potential, refractive index (RI), and free-thaw kinetic stability. They were investigated for percent removal efficiency (%RE) of RIF from the bulk aqueous solution for varied time intervals (10–60 min). Finally, scanning electron microscopy–energy dispersive x-ray (SEM–EDX) and inductive coupled plasma–optical emission system (ICP–OE) were used to confirm the extraction of trace content of dimethyl sulfoxide (DMSO) and others in the treated water. Considering the data obtained for globule size, PDI, viscosity, zeta potential, freeze–thaw stability, and refractive index, NF5 was the most suitable for RIF removal. The largest %RE value (91.7%) was related to NF5, which may be prudent to correlate with the lowest value (~39 nm) of size (maximum surface area available for contact adsorption), PDI (0.112), and viscosity (82 cP). Moreover, %RE was profoundly influenced by the content of CMC8 and the aqueous phase. These two phases had immense impact on the viscosity, size, and RI. The percent content of water, Smix, and CMC8 were 15% w/w), 60% w/w, and 25% w/w, respectively in NF5. SEM–EDX and ICP–OE confirmed the absence of DMSO and other hydrophilic components in the treated water. Thus, efficient NF5 could be a promising option to the conventional method to decontaminate the polluted aqueous system.