Objective To investigate the effects of nicorandil combined with metoprolol on cardiac function and heart rate variability in patients with ischemic cardiomyopathy (ICM). Methods A total of 72 ICM patients who were treated in Kaifeng Third People"s Hospital from February 2022 to March 2024 were selected and divided into a control group and an observation group according to different treatment methods.Among them, 37 cases were given metoprolol as the control group, and 35 cases were given nicorandil combined with metoprolol as the observation group. The clinical efficacy and adverse reaction rates of the two groups were compared, as well as the cardiac function [stroke volume (SV), left ventricular end-systolic diameter (LVESd), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF)], heart rate variability [root mean square of successive differences (rMSSD), standard deviation of NN intervals (SDNN), percentage of NN intervals with a difference of >50 ms (pNN50%), standard deviation of average NN intervals (SDANN)], serum inflammatory factors [high-sensitivity C-reactive protein (hs-CRP), matrix metalloproteinase (MMP)-9, interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1] levels before and after 3 months of treatment. Results The total effective rate of the observation group was 91.43%, which was higher than 70.27% of the control group (P<0.05). After 3 months of treatment, the levels of LVESD and LVEDD in the observation group were decreased more than those in the control group, and the levels of SV and LVEF in the observation group were increased more than those in the control group (P<0.05). The levels of RMSSD, SDNN, pNN50% and SDANN in the observation group were higher than those in the control group after 3 months of treatment (P<0.05). The levels of hs-CRP, MMP-9, IL-6 and MCP-1 in the observation group were lower than those in the control group after 3 months of treatment (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Nicorandil combined with metoprolol has significant therapeutic effects on ICM, not only improving cardiac function and regulating heart rate variability, but also reducing inflammatory response in the body, which is safe and reliable.