INTRODUCTION: There has been a rapid proliferation of synthetic nicotine products in recent years, despite newly established regulatory authority and limited research into its health risks. Previous research has implicated social media platforms as an avenue for nicotine product unregulated sales. Yet, little is known about synthetic nicotine product content on social media. We utilized natural language processing to characterize the sales of synthetic nicotine products on Instagram. METHODS: We collected Instagram posts by querying Instagram hashtags (eg, #tobaccofreenicotine) related to synthetic nicotine. Using Bidirectional Encoder Representations from Transformers, collected posts were categorized into thematically related topic clusters. Posts within topic clusters relevant to study aims were then manually annotated for variables related to promotion and selling (eg, cost discussion, contact information for offline sales). RESULTS: A total of 7425 unique posts were collected with 2219 posts identified as related to promotion and selling of synthetic nicotine products. Nicotine pouches (52.9%, n = 1174), electronic nicotine delivery systems (30.6%, n = 679), and flavored e-liquids (14.1%, n = 313) were most commonly promoted. About 16.1% (n = 345) of posts contained embedded hyperlinks and 5.8% (n = 129) provided contact information for purported offline transactions. Only 17.6% (n = 391) of posts contained synthetic nicotine-specific health warnings. CONCLUSIONS: In the United States, synthetic nicotine products can only be legally marketed if they have received premarket authorization from the Food and Drug Administration (FDA). Despite these prohibitions, Instagram appears to be a hub for potentially unregulated sales of synthetic and tobacco-free products. Efforts are needed by platforms and regulators to enhance content moderation and prevent unregulated online sales of existing and emerging synthetic nicotine products. IMPLICATIONS: There is limited clinical understanding of synthetic nicotines unique health risks and how these novel products are changing over time due to regulatory oversight. Despite synthetic nicotine-specific regulatory measures, such as the requirement for premarket authorization and FDA warning letters issued to unauthorized sellers, access to and promotion of synthetic nicotine is widely occurring on Instagram, a platform with over 2 billion users and one that is popular among youth and young adults. Activities include direct-to-consumer sales from questionable sources, inadequate health warning disclosure, and exposure with limited age restrictions, all conditions necessary for the sale of various tobacco products. Notably, the number of these Instagram posts increased in response to the announcement of new FDA regulations. In response, more robust online monitoring, content moderation, and proactive enforcement are needed from platforms who should work collaboratively with regulators to identify, report, and remove content in clear violation of platform policies and federal laws. Regulatory implementation and enforcement should prioritize digital platforms as conduits for unregulated access to synthetic nicotine products and other future novel and emerging tobacco products.