Background: Cardiovascular diseases, including coronary heart disease (CHD), are currently positioned among the leading causes of mortality globally. Risk factors of CHD include, among others, hypercholesterolemia and elevations in systemic inflammation. Functional foods enriched with compounds showing cholesterol-lowering effects are considered one among various dietary and lifestyle intervention strategies to tackle this problem. A CHD-preventive effect of dietary plant sterols has been broadly discussed, not only due to their ability to reduce blood cholesterol level, but also to their proven anti-inflammatory potential. Palm oil is one of the most widely consumed edible oils in the world. Despite its widespread use, especially in Asian countries, no study has been conducted using palm oil as a vehicle for plant sterols. Methods: The aim of the placebo-controlled double-blinded trial presented here was, therefore, to evaluate the effect of palm oil enriched with plant sterols, used as a cooking oil, on lipid profile and systemic inflammation marker in 100 adult hyperlipidemic residents of Bogor, Indonesia. Results: The study has shown a significant reduction in total cholesterol and LDL cholesterol level in study subjects consuming plant sterol-enriched palm oil as a replacement for usual palm oil for cooking, with no similar effect on CRP levels. Conclusions: The study suggests that, along with a healthy diet and lifestyle promotion, incorporating plant sterols in palm oil used for cooking may be an effective strategy to reduce cardiovascular risks in hyperlipidemic individuals.