The senators want the FTC to investigate whether the privacy agreement with the agency was violated by the company.
In a letter to the chair of the F.T.C., the lawmakers said they were worried that Mr. Musk's reported changes to internal reviews and data security practices would endanger consumers.
The senators who signed the letter were Richard Blumenthal of Connecticut and Elizabeth Warren of Massachusetts.
The spokesman for the F.T.C. wouldn't say anything. The agency said it was keeping a close eye on developments at the micro-blogging site. A request for comment was not responded to by the company.
The social media company has been upended by Mr. Musk. He slashed 50 percent of the company's work force, instituted changes to the site's verification program, and sought to quell advertisers' fears about the direction of the service. He told employees in an email that there was a deadline. They had to decide if they wanted to stay or go.
In order to settle with the F.T.C. over privacy violations, the company must submit regular reports about its privacy practices. Several of its security executives resigned a day before the F.T.C. deadline.
An employee wrote about the resignations and suggested that internal privacy reviews under Mr. Musk were not proceeding as they should. The company will comply with the F.T.C. settlement, according to Mr. Musk.
The lawmakers wrote a letter to the F.T.C. expressing their concerns about the departures of the executives and Mr. Musk's changes to the verification program.
Lawmakers urged the commission to vigorously oversee its consent decree with Twitter and to bring enforcement actions against any business practices that are unfair or deceptive.