Objective To investigate the value of time-intensity curve peak intensity (TIC-P), time-intensity curve mean intensity (TIC-M), peak of the fitting curve (FC-P), sharpness of the fitting curve (FC-S), and area under the fitting curve (FC-AUC) combined with serum homocysteine (Hcy) and high-sensitivity C-reactive protein (hs-CRP) in predicting ischemic stroke (ICS). Methods A total of 196 patients who were found to have carotid atherosclerosis by carotid artery ultrasound in Danzhou People's Hospital were enrolled, and according to the presence or absence of ICS, they were divided into ICS group with 91 patients and non-ICS group with 105 patients. The baseline data of each group were recorded, contrast-enhanced ultrasound was performed, and Hcy and hs-CRP levels were measured. The receiver operating characteristic (ROC) curve was used to analyze the value of quantitative parameters of contrast-enhanced ultrasound, Hcy, and hs-CRP in predicting the development of ICS. Results The ICS group had significantly higher quantitative parameters of carotid plaque contrast-enhanced ultrasound, TIC-P, TIC-M, FC-P, FC-S, and FC-AUC, than the non-ICS group (P<0.05). The ICS group had significantly higher Hcy and hs-CRP levels than the non-ICS group (P<0.01). The ROC curve analysis showed that combined measurement of quantitative parameters, Hcy, and hs-CRP had a significantly higher area under the ROC curve in predicting ICS than quantitative parameters, Hcy, or hs-CRP measured alone[0.986 (95%CI:0.940-0.998) vs 0.890 (95%CI:0.830-0.951)/0.827 (95%CI:0.770-0.885)/0.795 (95%CI:0.737-0.856)], and combined measurement of the three indices had a sensitivity of 98.5% and a specificity of 93.6% in predicting ICS. The correlation analysis showed that in the patients with ICS, FC-AUC was well correlated with Hcy and hs-CRP (r=0.815 and 0.792, P<0.001). Conclusions Contrast-enhanced ultrasound quantitative parameters combined with Hcy and hs-CRP levels can accurately predict the development of ICS.