The former first daughter criticised the Mr Trump's travel ban and posted a series of concerned messages about the planned repeal of Obamacare.
She also had a strong message following reports a Sikh man was told to "go back to your own country", tweeting: "This is his country. This is our country."
Ms Clinton, whose mother Hillary was defeated by Mr Trump in the recent presidential election, also took on White House Press Secretary, Sean Spicer, after he claimed that the US leader meant something else because he used quotation marks when accusing Barack Obama of "wire tapping" him.
She said: "Is the lesson that we should put in 'quotes' things we don't mean? Rather than what we say (and mean)? Asking for ... the world".
The political bent to her tweets since the start of the year has lead some to suspect she may be eyeing a run for office, according to The Hill.
A former aide to Hillary Clinton told the news site: "She’s never denied that she has an interest in running for office, and that leads me to believe that one day she will. And she’d probably be successful."
Ms Clinton told Sky News two years ago that she would "absolutely" consider running for election "one day" if she believed she could make a difference.
She would be following in the footsteps of her parents who have held a state governorship, a Senate seat, the post of Secretary of State and the Presidency between them.
But the 37-year-old gave a forceful "No" in response to rumours circulating last month that she would go for the Senate seat of New York's Kirsten Gillibrand if the latter stood for President in 2020.
Her mother held the same seat for eight years before moving to the State Department in 2009.
Her chief of staff, Bari Lurie, also told The Hill: "She is not running."
Whether or not she will continue the dynasty created by her parents, Ms Clinton, who is vice chair of the Clinton Foundation, is without doubt politically active.
In January she took her young daughter to a protest in New York against Mr Trump's first travel ban, and tweeted: "We will keep standing up for a country that matches our values and ideals for all".
She has also spoken out about the rights of LGBT people following a policy shift under Mr Trump that saw federal guidance on the use of toilets and locker rooms rolled back.