Solubilizing adjuvants are commonly used to dissolve insoluble drugs. However, the application of solubilizing adjuvants has many disadvantages, such as biocompatibility, biodegradability, toxicity, irritation, and environmental problems. To overcome these problems, gelatin and oleic acid sodium salt (OAS), a generally recognized as safe-listed material were chosen to develop a natural solubilizing adjuvant using the fattigation platform technology when simply mixed with poorly water-soluble drugs. We synthesized the gelatin and OAS conjugates (GOC) at three different ratios (1:1, 1:3, 1:5; GOC 1, GOC 2, and GOC 3, respectively) via the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide reaction using a spray dryer. This amphiphilic micronized GOC was self-assembled into nanoparticles. The synthesis of new amphiphilic conjugates was identified through fourier transform-infrared (FT-IR) spectroscopy. All GOCs showed good wettability, indicating that their amphiphilic nature. GOCs were also found to be non-porous. The powder properties of the GOCs, such as angle of repose, bulk density, and tapped density were varied with the oleic acid bonding ratio. Then, GOCs were utilized to investigate the enhanced solubility and dissolution rate of various poorly water-soluble drugs such as cilostazol (CSZ), coenzyme Q10, ticagrelor, telmisartan, aprepitant and itraconazole as model drugs. Based on the solubility studies by concentration and type of GOCs, 3% GOC 2 was selected. When this GOC mixed with these model drugs by a physical mixture, the wet method and by hot melting, the solubility was highly enhanced compared to the pure control drug, ranging from 20-150,000 times. In case of CSZ, all formulations significantly improved dissolution rate compared to the CSZ alone and the reference tablet, cilostan® (Korea United Pharm) in simulated intestinal fluid containing 0.2% sodium lauryl sulfate. Differential scanning calorimetry and powder X-ray diffraction were conducted to confirm the crystal polymorphic structure of CSZ, and as a result they changed to diminutive peak intensity compared to CSZ alone. Field-emission scanning electron microscopy indicated that GOC was spherical with a reduced size of about 100 nm. The reduction of drug particles via nanonization and self-assembly of amphiphilic GOC in an aqueous media could be a key factor to improve poor water solubility by providing a favorable dispersion of drug molecules in an amphiphilic network.