Palabra de Mujer follows the interconnected lives of four women from varied social backgrounds in Mexico City: Vanesa, Fernanda, Paulina and Matilde, all of whom work for a production company that is producing a television talk show that shares the same name as the series.

The plot begins as Vanesa approaches a female friend, Delia, to help her establish a production company to produce quality programming for women with Fernanda, Paulina, Matilde and Irmita supporting the business venture.

The television program they seek to produce becomes the motivation that Vanesa needs to rebuild her life after Julian, her husband of 22 years, left her for a younger woman.

Vanesa lives with her two children, Clara and Emiliano, who are ignorant of the fact that many of the marital woes experienced by their mother and father were because they lost their first son 20 years earlier while vacationing in Spain.

Matilde is the creative genius who, though she hails from humbler origins (her father is a mechanic and her mother works in the market), balances her new professional life with her recent marriage to Robert, Delia's son.