ChemInformant is a Python client engineered for programmatic access to PubChem, specifically targeting high-throughput and automated data retrieval tasks. Its architecture streamlines the entire workflow from data acquisition to analysis by directly converting large, mixed-type lists of chemical identifiers into analysis-ready Pandas DataFrames. To ensure operational resilience, the package natively integrates a suite of robustness features, including persistent HTTP caching, automatic rate-limiting with exponential backoff retries, and runtime data validation using Pydantic. By systematically addressing critical limitations in existing tools—such as network instability and inefficient batch processing—and offering up to a 48-fold performance increase, ChemInformant delivers a significantly more reliable and efficient component for the modern Python cheminformatics ecosystem.