This study hypothesizes that phospholipid-based naturosoomal nanocarriers can significantly enhance the oral solubility and bioavailability of naringin (NARNs) by improving its absorption and pharmacokinetic profile. The NARNs were prepared using solvent evaporation techniques employing a quality-by-design approach followed by physicochemical (UV-visible spectroscopy, FTIR, DSC, XRD, SEM, TEM, PS, ZP analysis), functional (EE, apparent solubility, in-vitro drug release study) characterization and pharmacokinetic investigation. NARNs showed 91.15 ± 1.40% EE, with 12-fold aqueous solubility than the pure drug, i.e., naringin (NAR). The size of the NARNs vesicles was between 150 and 300 nm, demonstrating the controlled vesicle size, whereas the zeta potential and polydispersity index were -32.2 mV and 0.524, respectively signifying the excellent stability and homogeneity of naturosomal suspension. The NARNs in-vitro dissolution data demonstrated a superior release profile (92.12%) compared to pure NAR (38.90%) and physical mixture (43.72%). The pharmacokinetic parameters of NARN in the rabbit showed promising results (T = 2.0 h, C = 1.76 ± 0.10 µg/mL, and AUC = 14.22 ± 0.13 µg/mL h). Thus, overall results indicated that naturosomal drug delivery is a capable method for improving the drug release profile of NAR and oral bioavailability, reducing toxicity by minimizing dose size.