I don't think anyone can answer that without knowing the 2.1 speakers in question very well - not just the make/model, but knowing enough about how they are actually designed/engineered.
If the headphone jack on the speakers just directly passes the signal through, and uses good enough quality wiring etc... at all points there should be no difference at all.
If on the other hand the signal passes through some components within the speakers or gets transmitted through some wiring not properly shielded from interference or something it could introduce noise.
There are a couple of ways you could test though to be sure -
1) Listening test. Try both ways and see if you can hear any difference. Also rather than playing music or something, try with just silence but with the volume turned up high. If plugging in via the speakers introduces noise you might clearly hear a hum through the headphones against a background of silence.
2) Scientific test. Use RightMark Audio Analyzer (
https://audio.rightmark.org/index_new.shtml). How that works is you plug a cable from the speaker or headphone output into the microphone input, then run the test. It plays sound then measures what it gets back compared to what it sent, and gives you some numbers for things like signal to noise ratio. Run that twice - once with headphone out>mic in directly, and once with speaker out>speakers>headphone jack>mic in, and see if you get a significant difference.