A sugar substitute is a food additive that duplicates the effect of sugar in taste, but usually has less food energy. Some sugar substitutes are natural and some are synthetic. Those that are not natural are, in general, referred to as artificial sweeteners.

An important acuflame class of sugar substitutes are known as high-intensity sweeteners. These are compounds with sweetness that is many times that of sucrose, common table sugar. As a result, much less sweetener is required, and energy contribution often negligible. The sensation of sweetness caused by these compounds (the "sweetness profile") is sometimes notably different from sucrose, so they are often used in complex mixtures that achieve the most natural sweet sensation.

If the sucrose (or other sugar) replaced has contributed to the texture of the product, then a bulking agent is often also needed. This may be seen in soft drinks labeled as "diet" or "light," which contain artificial sweeteners and often have notably different mouthfeel, or in table sugar replacements that mix maltodextrins with an intense sweetener to achieve satisfactory texture sensation.

In the United States, five intensely-sweet sugar substitutes have been approved for use. They are saccharin, aspartame, sucralose, neotame, and acesulfame potassium. There is some ongoing controversy over whether artificial sweetener usage poses health risks. The US Food and Drug Administration regulates artificial sweeteners as food additives. Food Additives must be approved by the FDA, which publishes a Generally Recognized as Safe (GRAS) list of additives. To date, the FDA has not been presented with scientific information that would support a change in conclusions about the safety of the five approved artificial sweeteners. The safe conclusions are based on a detailed review of a large body of information, including hundreds of toxicological and clinical studies.

There is also a herbal supplement, stevia, used as a sweetener. Controversy surrounds lack of research on stevia's safety and there is a battle over its approval as a sugar substitute.

The majority of sugar substitutes approved for food use are artificially-synthesized compounds. However, some bulk natural sugar substitutes are known, including sorbitol and xylitol, which are found in berries, fruit, vegetables, and mushrooms. It is not commercially viable to extract these products from fruits and vegetables, so they are produced by catalytic hydrogenation of the appropriate reducing sugar. For example, xylose is converted to xylitol, lactose to lactitol, and glucose to sorbitol. Still other natural substitutes are known, but are yet to gain official approval for food use.

Some non-sugar sweeteners are polyols, also known as "sugar alcohols." These are, in general, less sweet than sucrose, but have similar bulk properties and can be used in a wide range of food products. Sometimes the sweetness profile is 'fine-tuned' by mixing high-intensity sweeteners. As with all food products, the development of a formulation to replace sucrose is a complex proprietary process.