Date (Phoenix dactylifera L.) pits are a by-product of the date processing industry and are being explored as a source of bioactive compounds within the framework of the circular economy. This study aimed to perform a preliminary safety screening of the in vivo toxicity and mutagenic potential of ethanolic extracts obtained from different date pit varieties. Extracts from Alig (DA), Deglet Nour (DDN), and Kentichi (DK) varieties were administered to Galleria mellonella larvae at different concentrations, and health indices and survival were monitored for 4 days. No significant toxicity was observed at concentrations up to the MIC (6.25 mg/mL), while higher doses (≥2 MIC) had moderate effects on larval viability. The mutagenic potential was evaluated for two extracts (DDN and DK) using the Ames test with Salmonella enterica serovar Typhimurium strains TA98 and TA100, in the absence of metabolic activation. Mutagenic index values were below 2.0 for all conditions tested, with the exception of DDN on TA98, where values consistently exceeded 2.0 without a clear dose–response relationship. Due to the absence of metabolic activation and the limited strain panel, the results should be interpreted as preliminary. Overall, the combined preliminary in vitro and in vivo initial findings suggest that ethanolic extracts of date pits do not exhibit an evident mutagenic or toxic effects at biologically relevant concentrations under the conditions tested, providing a basis for further safety evaluation towards their application in the food industry.