Manchester United striker Macheda, currently on loan at QPR, Newcastle forward Ranger and Walsall's Smith are accused of acting in a way which was "improper and/or brought the game into disrepute", including "a reference to a person's or persons' sexual orientation".
The three players have until 4pm on Wednesday to respond.
An FA statement today read: "Newcastle United's Nile Ranger, Walsall's Manny Smith and Manchester United's Federico Macheda, currently on loan at Queens Park Rangers, have all been charged with improper conduct in relation to comments made on Twitter.
"The charge is that the players acted in a way which was improper and/or brought the game into disrepute.
"It is further alleged that the breach included a reference to a person's or persons' sexual orientation.
"Each has until 4pm on Wednesday 29 February 2012 to respond to the charge."
West Ham midfielder Ravel Morrison was last week fined £7,000 by the FA in response to a homophobic remark made on Twitter.
Morrison, who completed an undisclosed switch to Upton Park from Manchester United at the end of January, is reported to have made the comment in response to another Twitter user.
The 19-year-old was also warned as to his future conduct by the FA.