The object of this study was to investigate the influence of hydroxypropylmethylcellulose (HPMC) and sodium lauryl sulfate (SLS) on the solubility, dissolution, and crystallinity of poorly water‐soluble sirolimus in solvent‐evaporated solid dispersions. For the selection of suitable carriers, the influence of carriers on the solubility of sirolimus was identified. Among the carriers tested, HPMC and SLS gave most improved drug solubility, resulting in selecting them as a suitable polymer and surfactant, respectively. Numerous solvent‐evaporated solid dispersions were prepared with various ratios of sirolimus, SLS, and HPMC via the spray‐drying system. Then, their aqueous solubility, dissolution, and crystallinity were evaluated. All generated formulations significantly enhanced the solubility and dissolution of drug when compared with the sirolimus powder. As the amount of HPMC and SLS were increased, the solubility and dissolution in solvent‐evaporated solid dispersions were increased. Moreover, all the solid dispersions represented the amorphous form of drug. Among the solid dispersions evaluated, the solid dispersion consisted of sirolimus, HPMC, and SLS at the weight ratio of 1:5:0.1 had most improved aqueous solubility (350.83 ± 11.92 vs. 0.003 ± 0.001 μg/mL) and dissolution (12.58 ± 1.31 vs. 1.13 ± 0.60%, at 240 min) compared with drug powder, respectively. This solvent‐evaporated solid dispersion appeared as the round‐shape and reduced the particle sizes. Thus, HPMC and SLS considerably affected the solubility and dissolution. Furthermore, this novel solvent‐evaporated solid dispersion would be a potential candidate for oral preparation of sirolimus.