To sanitize phone numbers before sending mass alerts, developers can use the Twilio Lookup API to validate and format phone numbers, checking for real phone numbers, correct formatting, and mobile line type. The API requires a Twilio account, Python helper library, and knowledge of ISO country codes. Two options are provided: normalizing phone numbers with national formatting to E.164 and checking validity, or running a phone number through the validation function of the API. Additionally, developers can check for mobile phone number types using carrier lookups, which may incur costs depending on the volume of requests. By sanitizing phone numbers, developers can reduce API errors and increase confidence in their systems.